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There is an ongoing debate on the apparent depletion of sulfur in the interstellar medium (ISM) compared to its universal abundance; therefore, the investigation of sulfurous compounds at low temperatures is of utmost importance. This work aims to study thioacetamide, H3C–C(=S)–NH2, in low-temperature inert Ar and para-H2 matrices by IR spectroscopy. The samples have been exposed to various sources of irradiation, such as Lyman-α or laser UV photons as well as energetic electrons. Using different host materials enabled assessing the matrix's impact on precursor decomposition. The response of the molecule to different types of irradiation has also been evaluated. The existence of three main decomposition channels were deduced: formation of (i) CH3, CH4, and HNCS; (ii) H2S and H2C=C=NH; and (iii) NH3 and H2C=C=S. The H3C–CN and H3C–NC isomers of H2C=C=NH could also be identified. Secondary products such as HNC and HCN were also detected in the quantum solid para-H2 in contrast to the more rigid Ar matrix. The listed decomposition products have been observed in the ISM, with the exception of H2C=C=NH and H3C–NC. The results point to the potential sensitivity of the precursor molecule to energetic radiation in space environments. Finally, the findings of this work will serve as a foundation for future irradiation experiments using the astrochemically more relevant pure thioacetamide ice. [ABSTRACT FROM AUTHOR]

In this study was investigated the effects of extract of the Juncus inflexus subsp. inflexus (JI) plant on thioacetimide (TAA)‐induced liver damage. Six experimental groups were formed using 42 8–12‐weeks old Sprague dawley male rats, with seven experimental animals per group. Liver tissue sections were examined by staining with hematoxylin eosin (H‐E), periodic acid schiff (PAS) and caspase‐3. On the other hand, the tissue homogenates were analyzed by enzyme linked immunosorbent assay (ELISA), in terms of malondialdehyde (MDA) and glutathione (GSH). Compared to other groups, it was observed that the MDA rose significantly in the TAA group and that the GSH fell and that the expression of the caspase‐3 was significantly increased. On the other hand, it was found that lipid peroxidation decreased significantly in the TAA + JI group when compared to JI + TAA group. Also, to see the antioxidant properties of the plant in detail, molecular dynamic simulations were done. The antioxidant property of 59.16% in extract compounds of JI was theoretically demonstrated. The antioxidant activity of the 10‐methoxy‐nb‐alpha‐methylcorynantheol molecule, which is found at the highest rate in the relevant plant, has been theoretically revealed for the first time. In conclusion, this study has revealed that the extraction obtained from the Juncus inflexus plant has protective and therapeutic properties for the liver. [ABSTRACT FROM AUTHOR]

This study assessed the possible pharmacological effects of Chlorella vulgaris (Cg), Spirulina platensis (St), and silymarin (Sl) against thioacetamide (TA)-induced cardiotoxicity in rats, with a focus on their antioxidant, cardioprotective, and anti-inflammatory properties. The following is the random grouping of sixty male rats into six groups of ten animals each: the control (negative control), TA-intoxicated group (positive control; 300 mg/kg body weight (BW)), Sl + TA group (100 mg Sl/kg BW + TA), St + TA group (400 mg St/kg BW + TA), Cg + TA (400 mg Cg/kg BW + TA), and St + Cg + TA group (400 St + 400 Cg mg/kg BW + TA) were all administered for 30 days. At the start of the study, groups 2 through 6 were administered TA intraperitoneally at a dosage of 300 mg/kg BW for two consecutive days, with a 24 h gap between each dose, to induce cardiac damage. Blood samples were obtained to measure hematological parameters and perform biochemical assays, including lipid profiles and cardiac enzymes. For histopathology and immunohistochemistry determination, tissue samples were acquired. The current findings showed that TA injection caused hematological alterations and cardiac injury, as evidenced by greater serum levels of troponin I, creatine kinase-MB, and total creatine kinase (p < 0.05), as well as significantly elevated serum malondialdehyde and decreased serum total antioxidant capacity (p < 0.05) concentrations. Moreover, an increase in blood low-density lipoprotein and total cholesterol concentration (p < 0.05) was recorded in the TA group. There were alterations in the heart tissue's histological structure of the TA group compared to the control ones. These alterations were characterized by vacuolar degeneration of myocytes, loss of cross striation, coagulative necrosis, and fibrosis of interstitial tissue, which was ameliorated by the supplementation of SI, St, and Cg. The TA-intoxicated group showed weak expression of B-cell lymphoma protein 2 (p < 0.05) and strong immunoreactivity of tumor necrosis factor-α and B-cell lymphoma protein 2-associated X (p < 0.05). However, the groups receiving Sl, St, and Cg experienced the opposite. The administration of Sl, St, Cg, and St + Cg along with TA significantly improved and restored (p < 0.05) erythrogram indices, including RBCs, hemoglobin, total leukocytic count, lymphocytes, and monocyte, to the normal control values. The administration of Sl, St, and Cg alleviated the cardiotoxicity caused by TA via reducing oxidative stress, inflammatory markers, and apoptosis in heart tissue. In summary, the current findings suggest that the treatment with Sl, St, and Cg was beneficial in ameliorating and reducing the cardiotoxicity induced by TA in rats. [ABSTRACT FROM AUTHOR]

A new strategy for thiochromen‐4‐one synthesis that relies on the denitrative formal [5+1] cycloaddition of 1‐(2‐nitrophenyl)‐2‐yn‐1‐ones with thioacetamide is described. Achieved under reaction conditions that did not require transition metal catalysis, nor the exclusion of air or moisture, the reaction is suggested to involve exploiting the propensity of thioacetamide to undergo hydrolysis under basic conditions. This is follows by addition of the ensuing sulfide anion to the 1,3‐alkynone and a nucleophilic aromatic substitution and denitrative rearomatization cascade to give the S‐heterocyclic product in yields of 41–99 %. [ABSTRACT FROM AUTHOR]

With the aim of producing new heterocycle molecules, the previously reported 2-(aminomethyl)-2-(4-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one was converted efficiently by reacting with N,N′-dithiocarbonyldiimidazole (DTCI) to produce the substituted imidazolidine-2-thione moiety inserted in a three-fused-ring scaffold of the title compound. The molecular composition was confirmed by a high-resolution MS experiment, and its structure was elucidated by 1H, 13CNMR, and IR analyses. The thioacetamide form of the product was supported by density functional theory (DFT)–NMR analysis where 13C chemical shifts of the thioacetamide form and of its iminothiol tautomer were calculated in chloroform at the BP86/Jgauss-TZP2 level of theory. The very strong linear correlation between 13C chemical shifts from experimental findings and by calculation for the NHC=S form confirmed the structure. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the impact of thioacetamide (TAA) on the structure and function of the testes and assess the therapeutic effects of Curcuma longa (Cl) against TAAinduced toxicity in rats. Materials and Methods: Thirty-two male albino rats weighing 180-200 gm and aged 11-12 weeks were randomly separated into four groups. The control group was given normal saline, the Cl group was orally administered Cl (500 mg/kg/day), the TAA group received intraperitoneal TAA (200 mg/kg body weight, three times/week), and the Cl with TAA group received Cl orally two hours before TAA administration. After 8 weeks, all rats were anesthetized, and body and testis weights were recorded. Morphological and histological assessments as well as biochemical analyses were conducted. Results: The study revealed a significant decrease in both body and testis weights in the TAA group, accompanied by a substantial increase in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and malondialdehyde (MDA) levels. Testosterone (T) and glutathione (GSH) were significantly decreased in the TAA-treated group compared to the control. Conversely, the Cl-treated group exhibited a substantial decrease in LH, FSH, and MDA levels while showing a significant increase in T and GSH. Conclusion: Cl has been found to have a potential therapeutic role in mitigating TAA-induced testicular damage by acting as an antioxidant. This is supported by a significant decrease in oxidative stress markers and supporting hormonal levels. Further research is needed to understand the underlying mechanisms and explore the clinical applicability of Cl in preventing and treating testicular toxicity. [ABSTRACT FROM AUTHOR]

Background: Thioacetamide (TAA) is known to cause damage to various organs, including the testes, posing a significant health threat. On the other hand, Curcuma longa (Cl) has been recognized for its antioxidant properties, suggesting a potential protective role against TAA-induced toxicity in the testes. Aim: This study aims to investigate the effect of TAA on testicular function and structure while exploring the therapeutic and protective potential of C. longa versus TAA toxicity. Methods: Thirty-two male albino rats, with an age range of 11–12 weeks and a weight range of 180-200 g, were randomly allocated into four distinct groups. The control group received normal saline, while the Cl group ingested Cl orally at a dose of 500 mg/kg daily. The TAA group, received TAA through intraperitoneal injections at a dose of 200 mg/kg body weight three times per week. Lastly, the Cl with TAA group received Cl orally 2 hours before the TAA injections. After 8 weeks of treatment, we anesthetized the rats and saved blood samples for biochemical analysis. Results: The study revealed significant alterations in various biochemical parameters in the TAA-treated group, as compared with the control. Specifically, there was a significant increase in bilirubin, albumin, cholesterol, triglyceride, very low-density lipoprotein (VLDL-C), white blood cells (WBCs), low-density lipoprotein cholesterol (LDL-C), and platelets (PLT) levels. Conversely, the Cl-treated group exhibited significant reductions in these parameters, along with notable increases in red blood cells (RBCs), high-density lipoprotein cholesterol (HDL-C), and hemoglobin (HB). Conclusion: C. longa demonstrates a protective effect on the testes against TAA-induced toxicity, potentially attributed to its antioxidant properties. This suggests a promising avenue for the use of Cl in mitigating the harmful effects of TAA on testicular function and structure. [Open Vet J 2024; 14(7.000): 1585-1595]

Portal vein thrombosis (PVT) is a challenging and controversial complication of cirrhosis. Experimental models that reproduce cirrhotic PVT and effective pharmacological therapies are limited. We aimed to investigate the nature course and mechanisms of PVT in cirrhosis. A novel PVT model was developed via two-step total portal vein ligation in healthy and thioacetamide (TAA)-cirrhotic rats. Circulating and liver-infiltrating neutrophils were isolated from individuals with cirrhosis to examine neutrophil extracellular traps (NETs) and explore their unique characteristics and implications in PVT-associated fibrosis in cirrhosis. We further validated macrophage–myofibroblast transition (MMT) via multiplex immunofluorescence and single-cell sequencing. In the experimental model, cirrhosis promoted PVT development and portal vein intimal thickening. Interestingly, cirrhosis promoted spontaneous resolution of PVT due to instability of thrombus structure, along with pulmonary and intrahepatic clots. NETs-MMT mediate cirrhotic PVT and PVT-associated fibrosis, including fibrotic thrombus remodeling and increased hepatic collagen deposition. Mechanistically, caspase-4-dependent activation of neutrophils and GSDMD mediated the formation of NETs. The extracellular DNA of NETs promoted TGF-β1/Smad3-driven MMT. Inhibiting GSDMD with disulfiram suppressed cirrhotic PVT and prevented associated fibrosis. The cirrhotic PVT model reflected the following three main characteristics of cirrhotic PVT: spontaneous resolution, immunothrombosis, and intimal fibrosis. Targeting NETs with GSDMD inhibitors may serve as a new therapeutic concept to treat cirrhotic PVT. [ABSTRACT FROM AUTHOR]

Background: Thioacetamide (TAA) is known to cause damage to various organs, including the testes, posing a significant health threat. On the other hand, Curcuma longa (Cl) has been recognized for its antioxidant properties, suggesting a potential protective role against TAA-induced toxicity in the testes. Aim: This study aims to investigate the effect of TAA on testicular function and structure while exploring the therapeutic and protective potential of C. longa versus TAA toxicity. Methods: Thirty-two male albino rats, with an age range of 11-12 weeks and a weight range of 180-200 g, were randomly allocated into four distinct groups. The control group received normal saline, while the Cl group ingested Cl orally at a dose of 500 mg/kg daily. The TAA group, received TAA through intraperitoneal injections at a dose of 200 mg/kg body weight three times per week. Lastly, the Cl with TAA group received Cl orally 2 hours before the TAA injections. After 8 weeks of treatment, we anesthetized the rats and saved blood samples for biochemical analysis. Results: The study revealed significant alterations in various biochemical parameters in the TAA-treated group, as compared with the control. Specifically, there was a significant increase in bilirubin, albumin, cholesterol, triglyceride, very low-density lipoprotein, white blood cells, low-density lipoprotein cholesterol, and platelets levels. Conversely, the Cl-treated group exhibited significant reductions in these parameters, along with notable increases in red blood cells, high-density lipoprotein cholesterol, and hemoglobin. Conclusion: C. longa demonstrates a protective effect on the testes against TAA-induced toxicity, potentially attributed to its antioxidant properties. This suggests a promising avenue for the use of Cl in mitigating the harmful effects of TAA on testicular function and structure. [ABSTRACT FROM AUTHOR]

Macrophage inhibitory factor (MIF) is a multipotent cytokine, involved in the inflammatory response to infections or injuries. This study investigates the role of MIF in liver fibrosis and the modulating effect of betaine on MIF in thioacetamide (TAA)-induced liver fibrosis. The wild-type and knockout MIF−/− C57BL/6 mice were divided into the following groups: control; Bet group, which received betaine; MIF−/−; MIF−/−+Bet; TAA group, which received TAA; TAA+Bet; MIF−/−+TAA; and MIF−/−+TAA+Bet group. After eight weeks of treatment, liver tissue was collected for further analysis. The results revealed that TAA-treated MIF-deficient mice had elevated levels of hepatic TGF-β1 and PDGF-BB, as well as MMP-2, MMP-9, and TIMP-1 compared to TAA-treated wild-type mice. However, the administration of betaine to TAA-treated MIF-deficient mice reduced hepatic TGF-β1 and PDGF-BB levels and also the relative activities of MMP-2, MMP-9 and TIMP-1, albeit less effectively than in TAA-treated mice without MIF deficiency. Furthermore, the antifibrogenic effect of MIF was demonstrated by an increase in MMP2/TIMP1 and MMP9/TIMP1 ratios. The changes in the hepatic levels of fibrogenic factors were confirmed by a histological examination of liver tissue. Overall, the dual nature of MIF highlights its involvement in the progression of liver fibrosis. Its prooxidant and proinflammatory effects may exacerbate tissue damage and inflammation initially, but its antifibrogenic activity suggests a potential protective role against fibrosis development. The study showed that betaine modulates the antifibrogenic effects of MIF in TAA-induced liver fibrosis, by decreasing TGF-β1, PDGF-BB, MMP-2, MMP-9, TIMP-1, and the deposition of ECM (Coll1 and Coll3) in the liver. [ABSTRACT FROM AUTHOR]

Purpose: The consistent use of metformin has been linked to a reduced incidence of neoplastic diseases among diabetic populations. As a preventive intervention, metformin may offer a more favorable risk-benefit profile. Here, we explored the efficacy of metformin in the primary prevention of cholangiofibrosis, which can precede the carcinogen-induced development of cholangiocarcinoma (CCA). Our objective was to assess the potential of metformin to act as an intervention prior to the onset of these conditions. Methods: A rat model of thioacetamide (TAA)-induced cholangiofibrosis was utilized to assess the impact of metformin on the induction process of cholangiocarcinoma (CCA). Liver tissues were harvested and analyzed histologically using light microscopy, complemented by a deep-learning convolutional neural network for enhanced evaluation. Additionally, RNA sequencing (RNA-seq) was performed to investigate the genetic alterations associated with metformin treatment in this TAA-induced cholangiofibrosis model. Results: In the rat model, the TAA control group exhibited an increased incidence and average count of cholangiofibrosis cases in the liver, with rates of 100 % and an average of 12.0, compared to the metformin-treated group, which showed an incidence of 70 % and an average of 3.3. Notably, the progression from normal cholangioles to cholangiofibrosis was associated with the upregulation of several proteins critical for metabolic processes and the tumor microenvironment. These alterations were significantly mitigated by metformin treatment. Conclusions: Long-term metformin use may offer protective benefits against cholangiofibrosis, partially by regulating metabolic processes and improving the tumor microenvironment.

Abstract Background Hepatorenal syndrome is a life-threatening medical complication of liver cirrhosis. Hepatic cirrhosis is commonly accompanied by rapid failure of renal functions. Thioacetamide (TAA) is a potent hepatotoxin and a class 2-type carcinogen. Ubiquinone (Coq10) and lactoferrin (LF) are potent antioxidants with antifibrotic and antiinflammatory effects. However, whether Coq10 and LF reduce the hepatorenal injury induced by TAA remains unclear. Here, we investigated the potential protective effect of both/or Coq10 and LF in ameliorating TAA-induced hepatorenal injury and the role of WNT4 gene expression in detecting TAA-induced renal injury in rats. Seventy healthy and mature male Sprague Dawley rats, weighting (200 g ± 20 g) and aging (4–6) weeks were randomly divided into seven groups (n = 10): control, Coq10, LF, TAA, TAA + Coq10, TAA + LF, and TAA + Coq10 + LF. The hepatorenal injury was induced through intraperitoneal (i.p.) injection of TAA (150 mg/kg/twice/weekly) for nine weeks. Coq10 (10 mg/kg/day) and LF (200 mg/kg/day) were orally administered for nine weeks. Results TAA induced marked hepatorenal damage, evident by the significant increase in the alanine aminotransferase (ALT), aspartate transaminase (AST), serum creatinine (SCr) activities, and the blood urea nitrogen (BUN) level. Besides, the significant increases in concentrations of malondialdehyde (MDA) and nitric oxide (NOx) together with significant decreases in the activities of catalase (CAT) and superoxide dismutase (SOD). The histopathological analysis of the TAA group showed obvious fibrosis, steatosis, and inflammation of the hepatic parenchyma as well as severe glomerular and tubular damage of the renal parenchyma. In addition, TAA induced marked ultrastructural alterations and up-regulation in the expression of the WNT4 gene in the kidney. Meanwhile, the biochemical, histopathological, and ultrastructural alterations were significantly decreased with significant down-regulation in the expression of WNT4 in the groups exposed to TAA and treated with Coq10 and LF. Conclusion Our data suggested that Coq10 and LF could have protective effects on TAA hepatorenal damage, through improving the hepatic and renal functions, reduction of oxidative stress, structural and ultrastructural alterations, besides down-regulation in the expression of WNT4.

Objective: This study aimed to investigate the impact of thioacetamide (TAA) on the structure and function of the testes and assess the therapeutic effects of Curcuma longa (Cl) against TAA-induced toxicity in rats. Materials and Methods: Thirty-two male albino rats weighing 180–200 gm and aged 11–12 weeks were randomly separated into four groups. The control group was given normal saline, the Cl group was orally administered Cl (500 mg/kg/day), the TAA group received intraperitoneal TAA (200 mg/kg body weight, three times/week), and the Cl with TAA group received Cl orally two hours before TAA administration. After 8 weeks, all rats were anesthetized, and body and testis weights were recorded. Morphological and histological assessments as well as biochemical analyses were conducted. Results: The study revealed a significant decrease in both body and testis weights in the TAA group, accompanied by a substantial increase in luteinizing hormone (LH), follicle-stimulating hor¬mone (FSH), and malondialdehyde (MDA) levels. Testosterone (T) and glutathione (GSH) were significantly decreased in the TAA-treated group compared to the control. Conversely, the Cl-treated group exhibited a substantial decrease in LH, FSH, and MDA levels while showing a significant increase in T and GSH. Conclusion: Cl has been found to have a potential therapeutic role in mitigating TAA-induced testicular damage by acting as an antioxidant. This is supported by a significant decrease in oxi¬dative stress markers and supporting hormonal levels. Further research is needed to understand the underlying mechanisms and explore the clinical applicability of Cl in preventing and treating testicular toxicity. [J Adv Vet Anim Res 2024; 11(3.000): 762-771]

Abstract Background Liver transplantation remains the only curative treatment for end-stage liver diseases. Unfortunately, there is a drastic organ donor shortage. Hepatocyte transplantation emerged as a viable alternative to liver transplantation. Considering their unique expansion capabilities and their potency to be driven toward a chosen cell fate, pluripotent stem cells are extensively studied as an unlimited cell source of hepatocytes for cell therapy. It has been previously shown that freshly prepared hepatocyte-like cells can cure mice from acute and chronic liver failure and restore liver function. Methods Human PSC-derived immature hepatic progenitors (GStemHep) were generated using a new protocol with current good manufacturing practice compliant conditions from PSC amplification and hepatic differentiation to cell cryopreservation. The therapeutic potential of these cryopreserved cells was assessed in two clinically relevant models of acute liver failure, and the mode of action was studied by several analytical methods, including unbiased proteomic analyses. Results GStemHep cells present an immature hepatic phenotype (alpha-fetoprotein positive, albumin negative), secrete hepatocyte growth factor and do not express major histocompatibility complex. A single dose of thawed GStemHep rescue mice from sudden death caused by acetaminophen and thioacetamide-induced acute liver failure, both in immunodeficient and immunocompetent animals in the absence of immunosuppression. Therapeutic biological effects were observed as soon as 3 h post-cell transplantation with a reduction in serum transaminases and in liver necrosis. The swiftness of the therapeutic effect suggests a paracrine mechanism of action of GStemHep leading to a rapid reduction of inflammation as well as a rapid cytoprotective effect with as a result a proteome reprograming of the host hepatocytes. The mode of action of GStemHep relie on the alleviation of inhibitory factors of liver regeneration, an increase in proliferation-promoting factors and a decrease in liver inflammation. Conclusions We generated cryopreserved and current good manufacturing practice-compliant human pluripotent stem cell-derived immature hepatic progenitors that were highly effective in treating acute liver failure through rapid paracrine effects reprogramming endogenous hepatocytes. This is also the first report highlighting that human allogeneic cells could be used as cryopreserved cells and in the absence of immunosuppression for human PSC-based regenerative medicine for acute liver failure.

Acute liver injury, there is a risky neurological condition known as hepatic encephalopathy (HE). Herbacetin is a glycosylated flavonoid with many pharmacological characteristics. The purpose of this study was to assess the ability of herbacetin to protect against the cognitive deficits associated with thioacetamide (TAA) rat model and delineate the underlying behavioral and pharmacological mechanisms. Rats were pretreated with herbacetin (20 and 40 mg/kg) for 30days. On 30th day, the rats were injected with TAA (i.p. 350 mg/kg) in a single dose. In addition to a histpathological studies, ultra-structural architecture of the brain, liver functions, oxidative stress biomarkers, and behavioral tests were evaluated. Compared to the TAA-intoxicated group, herbacetin improved the locomotor and cognitive deficits, serum hepatotoxicity indices and ammonia levels. Herbacetin reduced brain levels of malodialdeyde, glutamine synthetase (GS), tumor necrosis factor- alpha (TNF-α), interleukin 1 B (IL-1β), annexin v, and increased brain GSH, Sirtuin 1 (SIRT1), and AMP-activated kinase (AMPK) expression levels. Also, herbacetin improve the histopathological changes and ultra- structure of brain tissue via attenuating the number of inflammatory and apoptotic cells. Herbacetin treatment significantly reduced the toxicity caused by TAA. These findings suggest that herbacetin might be taken into account as a possible neuroprotective and cognitive enhancing agent due to its ability to reduce oxidative stress, inflammation and apoptosis associated with TAA. [ABSTRACT FROM AUTHOR]

Background: Hepatorenal syndrome is a life-threatening medical complication of liver cirrhosis. Hepatic cirrhosis is commonly accompanied by rapid failure of renal functions. Thioacetamide (TAA) is a potent hepatotoxin and a class 2-type carcinogen. Ubiquinone (Coq10) and lactoferrin (LF) are potent antioxidants with antifibrotic and antiinflammatory effects. However, whether Coq10 and LF reduce the hepatorenal injury induced by TAA remains unclear. Here, we investigated the potential protective effect of both/or Coq10 and LF in ameliorating TAA-induced hepatorenal injury and the role of WNT4 gene expression in detecting TAA-induced renal injury in rats. Seventy healthy and mature male Sprague Dawley rats, weighting (200 g ± 20 g) and aging (4–6) weeks were randomly divided into seven groups (n = 10): control, Coq10, LF, TAA, TAA + Coq10, TAA + LF, and TAA + Coq10 + LF. The hepatorenal injury was induced through intraperitoneal (i.p.) injection of TAA (150 mg/kg/twice/weekly) for nine weeks. Coq10 (10 mg/kg/day) and LF (200 mg/kg/day) were orally administered for nine weeks. Results: TAA induced marked hepatorenal damage, evident by the significant increase in the alanine aminotransferase (ALT), aspartate transaminase (AST), serum creatinine (SCr) activities, and the blood urea nitrogen (BUN) level. Besides, the significant increases in concentrations of malondialdehyde (MDA) and nitric oxide (NOx) together with significant decreases in the activities of catalase (CAT) and superoxide dismutase (SOD). The histopathological analysis of the TAA group showed obvious fibrosis, steatosis, and inflammation of the hepatic parenchyma as well as severe glomerular and tubular damage of the renal parenchyma. In addition, TAA induced marked ultrastructural alterations and up-regulation in the expression of the WNT4 gene in the kidney. Meanwhile, the biochemical, histopathological, and ultrastructural alterations were significantly decreased with significant down-regulation in the expression of WNT4 in the groups exposed to TAA and treated with Coq10 and LF. Conclusion: Our data suggested that Coq10 and LF could have protective effects on TAA hepatorenal damage, through improving the hepatic and renal functions, reduction of oxidative stress, structural and ultrastructural alterations, besides down-regulation in the expression of WNT4. [ABSTRACT FROM AUTHOR]

Background: TGF-β1 and SMAD3 are particularly pathogenic in the progression of renal fibrosis. Aim: This study aimed to evaluate the kidney protective potentials of silymarin (SM) and exosomes of mesenchymal stem cells against the nephrotoxin thioacetamide (TAA) in rats. Methods: 32 female rats were randomly assigned into four groups: the control group, the TAA group, the TAA + SM group, and the TAA + Exosomes group. The kidney homogenates from all groups were examined for expression levels of TGF-β receptors I and II using real-time PCR, expression levels of collagen type I and CTGF proteins using ELISA, and the expression levels of nuclear SMAD2/3/4, cytoplasmic SMAD2/3, and cytoplasmic SMAD4 proteins using the western blot technique. Results: Compared to the control group, the injection of TAA resulted in a significant increase in serum levels of urea and creatinine, gene expression levels of TβRI and TβRII, protein expression levels of both collagen I and CTGF proteins, cytoplasmic SMAD2/3 complex, and nuclear SMAD2/3/4 (p-value < 0.0001), with significantly decreased levels of the co-SMAD partner, SMAD4 (p-value < 0.0001). Those effects were reversed considerably in both treatment groups, with the superiority of the exosomal treatment regarding the SMAD proteins and the expression levels of the TβRI gene, collagen I, and CTGF proteins returning to near-control values (p-value > 0.05). Conclusion: Using in vitro and in vivo experimental approaches, the research discovered a reno-protective role of silymarin and exosomes of BM-MSCs after thioacetamide-induced renal fibrosis in rats, with the advantage of exosomes. [ABSTRACT FROM AUTHOR]

Liver cirrhosis is a silent disease in humans and is experimentally induced by many drugs and toxins as thioacetamide (TAA) in particular, which is the typical model for experimental induction of hepatic fibrosis. Thus, the objective of the present study was to elucidate the possible protective effects of lactéol® forte (LF) and quercetin dihydrate (QD) against TAA‐induced hepatic damage in male albino rats. Induction of hepatotoxicity was performed by TAA injection (200 mg/kg I/P, twice/ week) in rats. LF (1 × 109 CFU/rat 5 times/week) and QD (50 mg/kg 5 times/week) treated groups were administered concurrently with TAA injection (200 mg/kg I/P, twice/ week). The experimental treatments were conducted for 12 weeks. Hepatotoxicity was evaluated biochemically by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma‐glutamyl transferase (GGT) in the serum and histopathologically with the scoring of histopathological changes besides histochemical assessment of collagen by Masson's trichrome and immunohistochemical analysis for α‐smooth muscle actin (α‐SMA), Ki67 and caspase‐3 expression in liver sections. Our results indicated that LF and QD attenuated some biochemical changes and histochemical markers in TAA‐mediated hepatotoxicity in rats by amelioration of biochemical markers and collagen, α‐SMA, Ki67 and caspase3 Immunoexpression. Additionally, LF and QD supplementation downregulated the proliferative, necrotic, fibroblastic changes, eosinophilic intranuclear inclusions, hyaline globules and Mallory‐like bodies that were detected histopathologically in the TAA group. In conclusion, LF showed better hepatic protection than QD against TAA‐induced hepatotoxicity in rats by inhibiting inflammatory reactions with the improvement of some serum hepatic transaminases, histopathological picture and immunohistochemical markers. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatic encephalopathy (HE) is a major neurological condition that occurs following acute or chronic liver failure. There are two types of HE: acute (Type A) and chronic (Type C). The acute form leads to rapid coma and death due to increased intracranial pressure, while neurobehavioral abnormalities potentially characterize the chronic form. There is currently no available treatment to regress or cure HE. This may be due to various factors, of which age and sex are the most important to consider when treating patients with HE. Accordingly, we examined whether sex and age play a role in the development of HE. We found that drug-induced (thioacetamide, TAA) brain edema was more severe in aged males than in young males or young/aged female rats. Furthermore, adding alcohol to the young male or young/aged female rats aggravated the brain edema. Regarding the behavioral changes, TAA-induced deficits were less pronounced in young and aged females than in aged males, whereas in the chronic type, young and aged males showed no behavioral changes when alcohol was infused along with TAA despite the severe brain edema and death that occurred. These findings suggest that aged males and young/aged females are more prone to developing brain edema in the presence of one or more liver toxins. Hepatic encephalopathy (HE) is a neurological condition linked to liver failure. Acute HE (Type A) occurs with acute liver failure, while chronic HE (Type C) is tied to cirrhosis and portal hypertension. HE treatments lag due to gaps in understanding its development by gender and age. We studied how sex and age impact HE and its severity with combined liver toxins. Our findings indicate that drug-induced (thioacetamide, TAA) brain edema was more severe in aged males than in young males or young/aged female rats. However, adding alcohol (ethanol, EtOH) worsens TAA's brain edema in both young and aged females, with females experiencing a more severe effect than males. These patterns also apply to Type A HE induced by azoxymethane (AZO) in mice. Similarly, TAA-induced behavioral deficits in Type C HE were milder in young and aged females than in males. Conversely, EtOH and TAA in young/aged males led to severe brain edema and fatality without noticeable behavioral changes. TAA metabolism was slower in aged males than in young or middle-aged rats. When TAA-treated aged male rats received EtOH, there was a slow and sustained plasma level of thioacetamide sulfoxide (TASO). This suggests that with EtOH, TAA-induced HE is more severe in aged males. TAA metabolism was similar in young, middle-aged, and aged female rats. However, with EtOH, young and aged females experience more severe drug-induced HE as compared to middle-aged adult rats. These findings strongly suggest that gender and age play a role in the severity of HE development and that the presence of one or more liver toxins may aggravate the severity of the disease progression. [ABSTRACT FROM AUTHOR]

Background and Objectives: TAA is potent hepatic/renal toxicant. Conversely, WGO is a potent dietary supplement with impressive antioxidant properties. Olmutinib is an apoptotic chemotherapy drug that does not harm the liver or kidney. This study investigated the impact of olmutinib and wheat germ oil (WGO) on Thioacetamide (TAA)-induced gene alterations in mice liver and kidney tissues. Materials and Methods: Adult male C57BL/6 mice were exposed to 0.3% TAA in drinking water for 14 days, followed by the oral administration of olmutinib (30 mg/kg) and WGO (1400 mg/kg) for 5 consecutive days. Treatment groups included the following: groups I (control), II (TAA-exposed), III (TAA + olmutinib), IV (TAA + WGO), and V (TAA + olmutinib + WGO). Results: The findings revealed that TAA exposure increased MKi67 and CDKN3 gene expression in liver and kidney tissues. Olmutinib treatment effectively reversed these TAA-induced effects, significantly restoring MKi67 and CDKN3 gene expression. WGO also reversed MKi67 effects in the liver but exhibited limited efficacy in reversing CDKN3 gene alterations induced by TAA exposures in both the liver and kidney. TAA exposure showed the tissue-specific expression of TP53, with decreased expression in the liver and increased expression in the kidney. Olmutinib effectively reversed these tissue-specific alterations in TP53 expression. While WGO treatment alone could not reverse the gene alterations induced by TAA exposure, the co-administration of olmutinib and WGO exhibited a remarkable potentiation of therapeutic effects in both the liver and kidney. The gene interaction analysis revealed 77.4% of physical interactions and co-localization between MKi67, CDKN3, and TP53 expressions. Protein–protein interaction networks also demonstrated physical interactions between MKi67, TP53, and CDKN3, forming complexes or signaling cascades. Conclusions: It was predicted that the increased expression of the MKi67 gene by TAA leads to the increase in TP53, which negatively regulates the cell cycle via increased CDKN3 expression in kidneys and the restoration of TP53 levels in the liver. These findings contribute to our understanding of the effects of olmutinib and WGO on TAA-induced gene expression changes and highlight their contrasting effects based on cell cycle alterations. [ABSTRACT FROM AUTHOR]

Animal studies are typically utilized to understand the complex mechanisms associated with toxicant-induced hepatotoxicity. Among the alternative approaches to animal studies, in vitro pooled human hepatocytes have the potential to capture population variability. Here, we examined the effect of the hepatotoxicant thioacetamide on pooled human hepatocytes, divided into five lots, obtained from forty diverse donors. For 24 h, pooled human hepatocytes were exposed to vehicle, 1.33 mM (low dose), and 12 mM (high dose) thioacetamide, followed by RNA-seq analysis. We assessed gene expression variability using heat maps, correlation plots, and statistical variance. We used KEGG pathways and co-expression modules to identify underlying physiological processes/pathways. The co-expression module analysis showed that the majority of the lots exhibited activation for the bile duct proliferation module. Despite lot-to-lot variability, we identified a set of common differentially expressed genes across the lots with similarities in their response to amino acid, lipid, and carbohydrate metabolism. We also examined efflux transporters and found larger lot-to-lot variability in their expression patterns, indicating a potential for alteration in toxicant bioavailability within the cells, which could in turn affect the gene expression patterns between the lots. Overall, our analysis highlights the challenges in using pooled hepatocytes to understand mechanisms of toxicity. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation remains the only curative treatment for end-stage liver diseases. Unfortunately, there is a drastic organ donor shortage. Hepatocyte transplantation emerged as a viable alternative to liver transplantation. Considering their unique expansion capabilities and their potency to be driven toward a chosen cell fate, pluripotent stem cells are extensively studied as an unlimited cell source of hepatocytes for cell therapy. It has been previously shown that freshly prepared hepatocyte-like cells can cure mice from acute and chronic liver failure and restore liver function. Methods: Human PSC-derived immature hepatic progenitors (GStemHep) were generated using a new protocol with current good manufacturing practice compliant conditions from PSC amplification and hepatic differentiation to cell cryopreservation. The therapeutic potential of these cryopreserved cells was assessed in two clinically relevant models of acute liver failure, and the mode of action was studied by several analytical methods, including unbiased proteomic analyses. Results: GStemHep cells present an immature hepatic phenotype (alpha-fetoprotein positive, albumin negative), secrete hepatocyte growth factor and do not express major histocompatibility complex. A single dose of thawed GStemHep rescue mice from sudden death caused by acetaminophen and thioacetamide-induced acute liver failure, both in immunodeficient and immunocompetent animals in the absence of immunosuppression. Therapeutic biological effects were observed as soon as 3 h post-cell transplantation with a reduction in serum transaminases and in liver necrosis. The swiftness of the therapeutic effect suggests a paracrine mechanism of action of GStemHep leading to a rapid reduction of inflammation as well as a rapid cytoprotective effect with as a result a proteome reprograming of the host hepatocytes. The mode of action of GStemHep relie on the alleviation of inhibitory factors of liver regeneration, an increase in proliferation-promoting factors and a decrease in liver inflammation. Conclusions: We generated cryopreserved and current good manufacturing practice-compliant human pluripotent stem cell-derived immature hepatic progenitors that were highly effective in treating acute liver failure through rapid paracrine effects reprogramming endogenous hepatocytes. This is also the first report highlighting that human allogeneic cells could be used as cryopreserved cells and in the absence of immunosuppression for human PSC-based regenerative medicine for acute liver failure. [ABSTRACT FROM AUTHOR]

For the emerging Sb2(S,Se)3 solar cells, most high‐efficiency devices employ a standard structure based on the heterojunction of weak n‐type Sb2(S,Se)3 and heavily n‐doped cadmium sulfide (CdS), and the sunlight is incident from the n‐type CdS side in either superstrate or substrate structure. The weak carrier extraction ability of the n–n heterojunction as well as the parasitic absorption and toxicity from CdS further limit the efficiency improvement and practical applications. Herein, for the first time, a strategy of treating manganese sulfide (MnS) with thioacetamide to enhance its p‐type conductivity is demonstrated, and a solar cell with inverted structure is constructed by forming a heterojunction with n‐type Sb2(S,Se)3. This inverted structure well overcomes the light absorption loss and toxicity elements in the standard structure. This post‐treatment effectively passivates the sulfur vacancy defects of MnS and in turn enables greater band bending in the heterojunctions for suppressed nonradiative recombination. Ultimately, the hole extraction ability of MnS shows essential improvement and enables a power conversion efficiency of 5.22% for the inverted Sb2(S,Se)3 solar cell. This study provides a proof‐of‐concept device structure for the preparation of high‐efficiency Sb2(S,Se)3 solar cells and offers new perspectives to achieve effective intrinsic doping of metal chalcogenides. [ABSTRACT FROM AUTHOR]

The response of the immune system to harmful stimuli leads to inflammation, and the adverse effects of the toxic hepatitis chemical, thioacetamide (TAA) on the human body are well documented. This article investigated the degree of protection provided by the combined pleotropic drug, metformin (Met) and the plant polyphenolic and the antiinflammatory compound, resveratrol (Res) on liver tissue exposed to TAA possibly via the inhibition of the inflammatory cytokine, tumor necrosis factor-α (TNF-α) / mammalian target of rapamycin (mTOR) axis-mediated liver fibrosis, as well as amelioration of profibrotic gene and protein expression. Rats were either given TAA (200 mg/kg via intraperitoneal injection) for 8 weeks beginning at the third week (experimental group) or received during the first two weeks of the experiment combined doses of metformin (200 mg/kg) and resveratrol (20 mg/kg) and continued receiving these agents and TAA until experiment completion at week 10 (treated group). A considerable damage to hepatic tissue in the experimental rats was observed as revealed by tissue collagen deposition in the portal area of the liver and a substantial increase (p<0.0001) in hepatic levels of the inflammatory marker, tumor necrosis factor-α (TNF-α), as well as blood levels of hepatocellular injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). TAA also augmented hepatic tissue levels of the signalling molecule that promotes liver fibrosis (mTOR), and profibrogenic markers; alpha-smooth muscle actin (α-SMA) protein, tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA, and matrix metalloproteinase-9 (MMP-9) mRNA. All these parameters were protected (p≤0.0016) by Met+Res. In addition, a significant correlation was detected between liver fibrosis score and inflammation, liver injury enzymes, mTOR, and profibrogenesis markers. Thus, these findings suggest that Met+Res effectively protect the liver against damage induced by thioacetamide in association with the downregulation of the TNF-α/mTOR/fibrosis axis. [ABSTRACT FROM AUTHOR]

This study assessed the possible pharmacological effects of Chlorella vulgaris (Cg), Spirulina platensis (St), and silymarin (Sl) against thioacetamide (TA)-induced cardiotoxicity in rats, with a focus on their antioxidant, cardioprotective, and anti-inflammatory properties. The following is the random grouping of sixty male rats into six groups of ten animals each: the control (negative control), TA-intoxicated group (positive control; 300 mg/kg body weight (BW)), Sl + TA group (100 mg Sl/kg BW + TA), St + TA group (400 mg St/kg BW + TA), Cg + TA (400 mg Cg/kg BW + TA), and St + Cg + TA group (400 St + 400 Cg mg/kg BW + TA) were all administered for 30 days. At the start of the study, groups 2 through 6 were administered TA intraperitoneally at a dosage of 300 mg/kg BW for two consecutive days, with a 24 h gap between each dose, to induce cardiac damage. Blood samples were obtained to measure hematological parameters and perform biochemical assays, including lipid profiles and cardiac enzymes. For histopathology and immunohistochemistry determination, tissue samples were acquired. The current findings showed that TA injection caused hematological alterations and cardiac injury, as evidenced by greater serum levels of troponin I, creatine kinase-MB, and total creatine kinase (p < 0.05), as well as significantly elevated serum malondialdehyde and decreased serum total antioxidant capacity (p < 0.05) concentrations. Moreover, an increase in blood low-density lipoprotein and total cholesterol concentration (p < 0.05) was recorded in the TA group. There were alterations in the heart tissue’s histological structure of the TA group compared to the control ones. These alterations were characterized by vacuolar degeneration of myocytes, loss of cross striation, coagulative necrosis, and fibrosis of interstitial tissue, which was ameliorated by the supplementation of SI, St, and Cg. The TA-intoxicated group showed weak expression of B-cell lymphoma protein 2 (p < 0.05) and strong immunoreactivity of tumor necrosis factor-α and B-cell lymphoma protein 2-associated X (p < 0.05). However, the groups receiving Sl, St, and Cg experienced the opposite. The administration of Sl, St, Cg, and St + Cg along with TA significantly improved and restored (p < 0.05) erythrogram indices, including RBCs, hemoglobin, total leukocytic count, lymphocytes, and monocyte, to the normal control values. The administration of Sl, St, and Cg alleviated the cardiotoxicity caused by TA via reducing oxidative stress, inflammatory markers, and apoptosis in heart tissue. In summary, the current findings suggest that the treatment with Sl, St, and Cg was beneficial in ameliorating and reducing the cardiotoxicity induced by TA in rats.

Highlights: Digital holography can realize the in situ observation of electrode/electrolyte interface and provide dynamic evolution information of the liquid phase of electrode, which is both efficient and effective in investing the interficial electrochemical mechanism and screening electrolyte additives. Thioacetamide electrolyte additive effectively enhances the electrochemical performance of Zn anode by regulating the interficial ion flux to induce dendrite-free Zn deposition and constructing adsorption molecule layers to inhibit side reactions. Zinc ion batteries are considered as potential energy storage devices due to their advantages of low-cost, high-safety, and high theoretical capacity. However, dendrite growth and chemical corrosion occurring on Zn anode limit their commercialization. These problems can be tackled through the optimization of the electrolyte. However, the screening of electrolyte additives using normal electrochemical methods is time-consuming and labor-intensive. Herein, a fast and simple method based on the digital holography is developed. It can realize the in situ monitoring of electrode/electrolyte interface and provide direct information concerning ion concentration evolution of the diffusion layer. It is effective and time-saving in estimating the homogeneity of the deposition layer and predicting the tendency of dendrite growth, thus able to value the applicability of electrolyte additives. The feasibility of this method is further validated by the forecast and evaluation of thioacetamide additive. Based on systematic characterization, it is proved that the introduction of thioacetamide can not only regulate the interficial ion flux to induce dendrite-free Zn deposition, but also construct adsorption molecule layers to inhibit side reactions of Zn anode. Being easy to operate, capable of in situ observation, and able to endure harsh conditions, digital holography method will be a promising approach for the interfacial investigation of other battery systems. [ABSTRACT FROM AUTHOR]

In the example of a rat model with chronic hepatoencephalopathy (HE), changes in the organ morphology of rats affect the balance of metabolites of the tricarboxylic acid (TCA) cycle and metabolites of the glutamine–glutamate (Gln-Glu) cycle, namely α-ketoglutarate (αKG) and α-ketoglutaramate (αKGM), as well as the enzymes associated with them, ω-amidase (ωA) and glutamine transaminase (GTK). This model of rats was obtained as a result of 2–22 weeks of consumption by animals of hepatotoxin thioacetamide (TAA) added to drinking water at a concentration of 0.4 g/L. The control (n = 26) and TAA-induced (n = 55) groups of rats consisted of 11 cohorts each. The control cohorts consisted of 2–4 rats, and the TAA-induced cohorts consisted of 4–7 individuals. Every two weeks, samples of blood plasma, liver, kidney, and brain tissues were taken from the next cohort of rats (a total of 320 samples). By the end of the experiment, irreversible morphological changes were observed in the organs of rats: the weight of the animals was reduced up to ~45%, the weight of the kidneys up to 5%, the brain up to ~20%, and the weight of the liver increased up to ~20%. The analysis revealed: (i) a decrease in the activity of ωA and GTK in the tissues of the brain, kidneys, and liver of rats with chronic HE (by ~3, 40, and 65% and ~10, 60, and 70%, respectively); and (ii) the appearance of a significant imbalance in the content of metabolites of the Gln-Glu cycle, αKG, and αKGM. It is indicative that a ~1.5–12-fold increase in the level of αKG in the blood plasma and tissues of the organs of rats with chronic HE was accompanied by a synchronous, ~1.2–2.5-fold decrease in the level of αKGM. The data obtained indicate an essential involvement of the Gln-Glu cycle in the regulation of energy metabolism in rats under conditions of chronic HE. Attention is focused on the significance of the αKG/αKGM ratio, which can act as a potential marker for diagnosing the degree of HE development. [ABSTRACT FROM AUTHOR]

Background: Several hepatotoxicants such as acetaminophen, carbon tetrachloride, and thioacetamide are repeatedly used to develop hepatic fibrosis to mimic the histological and hemodynamic characteristics of human illness. It may be a good idea to establish a better model among these hepatotoxicants to develop hepatic fibrosis. Aim: The present study evaluated comparative toxic effects of three model hepatotoxicants for experimental progression of fibrosis or cirrhosis. Materials and methods: Acetaminophen (200 mg/kg), carbon tetrachloride (200 µl/kg) and thioacetamide (200 mg/kg) were administered orally, thrice in a week for 8 weeks in different groups. After 8 weeks of exposure, animals were euthanized, blood and tissues were collected for various hematological, serological, tissue biochemical analysis and histological observations for comparative assessment of toxic consequences. Results: Significant deviation was noted in liver function tests, lipid peroxidation, glutathione, activities of superoxide dismutase, catalase, and GSH cycle enzymes; aniline hydroxylase, amidopyrine-N-demethylase, DNA fragmentation and level of hydroxyproline when compared with control group. Histology also depicted damage in liver histoarchitecture with exposure to acetaminophen, carbon tetrachloride and thioacetamide. Tukey's HSD post hoc test confirmed that thioacetamide produced severe toxic effects in comparison to carbon tetrachloride and acetaminophen. Conclusion: In conclusion, toxic effects were noted in ascending order as acetaminophen. [ABSTRACT FROM AUTHOR]

This research investigated if pitavastatin (Pita) might protect rats' kidneys against thioacetamide (TAA). By altering the PTEN/AKT/mTOR pathway, pitavastatin may boost kidney antioxidant capacity and minimize oxidative damage. Statins have several benefits, including antioxidant and anti-inflammatory characteristics. The principal hypothesis of this study was that Pita can regulate the miR-93/PTEN/AKT/mTOR pathways, which is thought to be responsible for its renoprotective effects. The experiment divided male rats into four groups. Group 1 included untreated rats as the control. Group 2 included rats which received TAA (100 mg/kg intraperitoneally thrice a week for two weeks) to destroy their kidneys. Groups 3 and 4 included rats which received Pita orally at 0.4 and 0.8 mg/kg for 14 days after TAA injections. Renal injury increased BUN, creatinine, and MDA levels and decreased glutathione (GSH) levels. Pitavastatin prevented these alterations. TAA decreased PTEN and increased miR-93, Akt, p-Akt, mTOR, and Stat3 in the kidneys. Pitavastatin also regulated the associated culprit pathway, miR-93/PTEN/Akt/mTOR. In addition, TAA induced adverse effects on the kidney tissue, which were significantly ameliorated by pitavastatin treatment. The findings suggest that pitavastatin can attenuate renal injury, likely by regulating the miR-93/PTEN/Akt/mTOR pathway. This modulation of the pathway appears to contribute to the protective effects of pitavastatin against TAA-induced renal injury, adding to the growing evidence of the pleiotropic benefits of statins in renal health. [ABSTRACT FROM AUTHOR]

This study examines In2S3 concentration to the photo‐induced current density of particulate In2O3–In2S3 composite heterostructures under visible light irradiation. A self‐templated approach involving hydrothermal sulfidation of In2O3 nanofibers with thioacetamide (TAA) in water produces the In2O3–In2S3 core–shell structure at a moderate temperature. The In2S3 fraction is readily tunable by adjusting the TAA concentration. Incorporating In2S3 (45–82 wt.%) leads to a decreased bandgap from 3.1 to ca. 2.3 eV, enabling the harvest of partial visible‐light energy to create charged carriers efficiently. The photocurrent is particularly pronounced when the In2O3–In2S3 composites consist of 45 wt.% In2S3, to which the photocurrent intensity is more significant than 0.1 mA⋅cm−2 at 0.8 V in 0.1 M Na2SO4 solution compared to less than 0.01 mA⋅cm−2 for the rest of the In2O3–In2S3 counterparts. This is attributable to the enhanced electron–hole separation at the semiconducting heterojunction and the more efficient use of the light spectrum due to the narrowing bandgap. [ABSTRACT FROM AUTHOR]

Iron overload has been recognized as a risk factor for liver disease; however, little is known about its pathological role in the modification of liver injury. The purpose of this study is to investigate the influence of iron overload on liver injury induced by two hepatotoxicants with different pathogenesis in rats. Rats were fed a control (Cont), 0.8% high-iron (0.8% Fe), or 1% high-iron diet (1% Fe) for 4 weeks and were then administered with saline, thioacetamide (TAA), or carbon tetrachloride (CCl4). Hepatic and systemic iron overload were seen in the 0.8% and 1% Fe groups. Twenty-four hours after administration, hepatocellular necrosis induced by TAA and hepatocellular necrosis, degeneration, and vacuolation induced by CCl4, as well as serum transaminase values, were exacerbated in the 0.8% and 1% Fe groups compared to the Cont group. On the other hand, microvesicular vacuolation induced by CCl4 was decreased in 0.8% and 1% Fe groups. Hepatocellular DNA damage was increased by iron overload in both models, whereas a synergistic effect of oxidative stress by excess iron and hepatotoxicant was only present in the CCl4 model. The data showed that dietary iron overload exacerbates TAA- and CCl4-induced acute liver injury with different mechanisms. [ABSTRACT FROM AUTHOR]

Thioacetamide (TAA)-induced hepatic encephalopathy (HE) has been reported in several studies. Sequel to acute or chronic liver failure, there is impairment in the hippocampal structure and hippocampal-mediated functions. The precise pathophysiological mechanism leading to neurological alterations remains elusive. The hippocampus also has rarely been examined in HE, hence this study. Vernonia amygdalina (VA) which possesses diverse biological activities has been studied and has promising therapeutic potential in several neurodegenerative diseases. Here, we investigated the neuroprotective activities of Vernonia amygdalina against thioacetamide-induced neuronal damage in the CA1 region of the hippocampus in the rat model. Thirty male Wistar rats were divided into five groups A-E (n=6). Group A (control) was the placebo and was administered 2mL/kg distilled water, group B was administered 100mg/kg thioacetamide only. Groups C-E were administered 100mg/kg of thioacetamide and were subsequently treated with 100mg/kg VA, 200mg/kg VA, and 3mg/kg vitamin C respectively. All administration was carried out for 14 days duration orally. Neurobehavioral tests were conducted. Required brain tissues for biochemical analyses were harvested following rat sacrifice. Glucose-6-phosphate dehydrogenase activity and hippocampal Glutamate levels were evaluated. Histological stains (H&E and cresyl violet) and immunohistochemical expression of Iba-1 protein (microglial marker) were used to assess neuroinflammation and neurodegeneration in the CA1 subfield. Statistical analyses were carried out using Graph pad prism 5 and all results were expressed as Mean±SEM. Means differences were identified by Tukey's post hoc test. Statistical significance was set at (p< 0.05). The neurobehavioral test results showed an observable increase in anxiety and impaired spatial working memory of the Wistar rats while glutamate (p = 0.6187; F =0.6844) and G6PDH activity (p = 0.6187; F= 0.9486) were not significantly different across groups. Thioacetamide treatment also resulted in neuroinflammation vis-à-vis microglial activation, causing neurodegeneration in the CA1 subfield. Vernonia amygdalina treatment ameliorated these neurotoxic changes. Altogether, Vernonia amygdalina treatment ameliorated thioacetamideinduced neurotoxicity in the CA1 region of the hippocampus via anti-neuroinflammatory and neuroprotective mechanisms. [ABSTRACT FROM AUTHOR]

Background. As a result of studying the synthesis and biological activity of condensed heterocyclic compounds, new drugs have been developed, including derivatives of 3-alkyl-2- methylquinazolin-4-one, and their bioactive derivatives have been identified. The development of new drugs based on them is relevant. Purpose. Development of a method for the synthesis of initial 2-methylquinazolin-4-ones by heterocyclization reaction and, on their basis, the synthesis of 3(H)-substituted 2-methylquinazolin-4-ones in the presence of alkylating agents. Determination of the structures of the obtained substances using IR, ¹H and 13C NMR methods. Methodology. 3-alkyl 2-methylquinazolin-4-ones were synthesized on the basis of 2- methylquinazolin-4-one (2,3-dimethylquinazolin-4-one and other compounds, they were studied by physical methods: IR, 1H and 13C NMR, factors influencing on the course of reactions. Originality. An improved method for the synthesis of 2-methylquinazolin-4-one has been developed using a heterocyclization reaction. New representatives of alkyl compounds have been synthesized. Findings. A method for the synthesis of 2-methylquinazolin-4-one with high yields has been developed, and new derivatives of 3-alkyl-2-methylquinazolin-4-ones based on this substance have been synthesized. Their structure has been studied by physical methods, and their compliance with the proposed structure has been proven. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE) is a central nervous system dysfunction syndrome caused by acute and chronic liver failure or various portal systemic shunt disorders. HE arises from metabolic disorder and excludes other known types of encephalopathy. HE is a major cause of death in people with liver disease. Early diagnosis and timely treatment are key to improving HE prognosis. Herein, we established a model of HE and performed metabolomics to identify 50 significantly differential metabolites between the HE group and control group. The main metabolic pathways associated with these differential metabolites were the purine metabolism, pyrimidine metabolism, aminoacyl tRNA biosynthesis, and glucose metabolism. Through proteomics analysis, we identified 226 significantly differential proteins (52 up-regulated and 174 down-regulated). The main (Kyoto Encyclopedia of Genes and Genomes) enrichment pathways were the Staphylococcus aureus infection, vitamin digestion and absorption, and complement and coagulation cascades. Through the conjoint analysis of proteomics and metabolomics, the differentially present proteins and metabolites were found to be involved in vitamin digestion and absorption, and ferroptosis pathways. In HE, malondialdehyde was significantly elevated, but glutathione was significantly diminished, and the redox balance was destroyed, thus leading to changes in proteins' levels associated with the ferroptosis pathway. In conclusion, this study preliminarily explored the molecular and metabolic mechanisms underlying HE. [ABSTRACT FROM AUTHOR]

Although curcumin possesses anti‐inflammatory, antioxidant, and cytoprotective qualities, its low absorption limits its medicinal uses. Before examining how curcumin influenced rats' liver fibrosis when thioacetamide (TAA) was produced, the current study employed nanoparticles (NPs) to improve curcumin bioavailability. Sixty mature rats were separated into six groups (Group 1, control; Group 2, curcumin; Group 3, curcumin nanoparticles; Group 4, TAA; Group 5, TAA + curcumin; Group 6, TAA + curcumin NPs). TAA administration caused considerable increases in serum liver enzymes associated with a remarkable depletion in the levels of albumin and total protein relative to the control. In addition, a significant elevation in malonaldehyde (MDA) level with a significant depletion in the antioxidant enzymes activity was detected. Also, TAA had a significant effect on the inflammation markers represented by the elevation in tumor necrosis factor (TNFα) and DNA damage. Administration of curcumin or curcumin NPs in TAA‐intoxicated rats significantly (p <.001, p <.0001) alleviates liver injury by correcting antioxidant status, inflammatory markers, and oxidative stress. The results of comparing TAA‐intoxicated rats treated with curcumin NPs to TAA‐intoxicated rats treated with bulk curcumin revealed that the ameliorative effect of nanocurcumin was stronger. These observations concluded that nanoparticle formulation can increase curcumin bioavailability and solubility, enhancing its antioxidant and anti‐inflammatory efficiency, resulting in greater potential against thioacetamide‐induced hepatotoxicity in rats. [ABSTRACT FROM AUTHOR]

Carbon dots (CDs) doped with heteroatoms have garnered significant interest due to their chemically modifiable luminescence properties. Herein, nitrogen- and sulfur-codoped carbon dots (NS-CDs) were successfully prepared using p-phenylenediamine and thioacetamide via a facile process. The as-developed NS-CDs had high photostability against photobleaching, good water dispersibility, and excitation-independent spectral emission properties due to the abundant amino and sulfur functional groups on their surface. The wine-red-colored NS-CDs exhibited strong green emission with a large Stokes shift of up to 125 nm upon the excitation wavelength of 375 nm, with a high quantum yield (QY) of 28%. The novel NS-CDs revealed excellent sensitivity for quercetin (QT) detection via the fluorescence quenching effect, with a low detection limit of 17.3 nM within the linear range of 0–29.7 μM. The fluorescence was quenched only when QT was brought near the NS-CDs. This QT-induced quenching occurred through the strong inner filter effect (IFE) and the complex bound state formed between the ground-state QT and excited-state NS-CDs. The quenching-based detection strategies also demonstrated good specificity for QT over various interferents (phenols, biomolecules, amino acids, metal ions, and flavonoids). Moreover, this approach could be effectively applied to the quantitative detection of QT (with good sensing recovery) in real food samples such as red wine and onion samples. The present work, consequently, suggests that NS-CDs may open the door to the sensitive and specific detection of QT in food samples in a cost-effective and straightforward manner. [ABSTRACT FROM AUTHOR]

Introduction: Thioacetamide is one of the organo-sulfur compound, their possible hazards are not fully studied. Overproduction of oxidant species is the main mechanism of Thioacetamide induced histological changes in many organs. Quercetin is a powerful antioxidant compound thereby may alleviate these effects. Aim of the Study: To assess the histological changes induced by Thioacetamide on adult male albino rat heart and lung as well as the probable role of Quercetin in attenuating these changes. Material and Methods: 24 adult male albino rats were divided into 3 equal groups: group I (Control group), group ΙΙ Thioacetamide group at a dose of 50 mg/kg/day and group ΙΙI received 50 mg/kg/day of thioacetamide and quercetin that was dissolved in distilled water. The rats were sacrificed after 28 days heart and lungs were harvested and fixed. Sections from both the heart and lungs were stained by Harris Hematoxylin & Eosin and Masson Trichrome stain. Sections from the heart were additionally stained for PAS. Sections from the lung were subjected to immunohistochemical staining for CD68. All sections were examined under light microscope. Further statistically analyzed and interpreted. Results: Thioacetamide administration result in more heart and lung injury score. Significant reduction in the injury score was found in Concomitant administration of quercetin with thioacetamide resulted in improvement in the structure of the lung and heart. Conclusion: Thioacetamide administration had a negative impact on both heart and lungs. meanwhile, quercetin exerted a protective effect when it was administrated with Thioacetamide. [ABSTRACT FROM AUTHOR]

In this work, we report the first attempt to investigate the dependence of thioacetamide (TAA) on the size of ZnO nanoparticles (NPs) in forming ZnS nanostructures from ZnO. Size-controlled B(blue)_, G(green)_, and Y(yellow)_ZnO quantum dots (QDs) and NC (nanocrystalline)_ZnO NPs were synthesized using a sol–gel process and a hydrothermal method, respectively, and then reacted with an ethanolic TAA solution as a sulfur source. ZnO QDs/NPs began to decompose into ZnS QDs through a reaction with TAA for 5~10 min, so rather than forming a composite of ZnO/ZnS, ZnO QDs and ZnS QDs were separated and remained in a mixed state. At last, ZnO QDs/NPs were completely decomposed into ZnS QDs after a reaction with TAA for 1 h irrespective of the size of ZnO QDs up to ~50 nm. All results indicate that ZnS formation is due to direct crystal growth and/or the chemical conversion of ZnO to ZnS. [ABSTRACT FROM AUTHOR]

Thioacetamide (TAA) within the liver generates hepatotoxic metabolites that can be induce hepatic fibrosis, similar to the clinical pathological features of chronic human liver disease. The potential protective effect of Albiflorin (ALB), a monoterpenoid glycoside found in Paeonia lactiflora Pall, against hepatic fibrosis was investigated. The mouse hepatic fibrosis model was induced with an intraperitoneal injection of TAA. Hepatic stellate cells (HSCs) were subjected to treatment with transforming growth factor-beta (TGF-β), while lipopolysaccharide/adenosine triphosphate (LPS/ATP) was added to stimulate mouse peritoneal macrophages (MPMs), leading to the acquisition of conditioned medium. For TAA-treated mice, ALB reduced ALT, AST, HYP levels in serum or liver. The administration of ALB reduced histopathological abnormalities, and significantly regulated the expressions of nuclear receptor-related 1 protein (NURR1) and the P2X purinoceptor 7 receptor (P2×7r) in liver. ALB could suppress HSCs epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, and pro-inflammatory factor level. ALB also remarkably up-regulated NURR1, inhibited P2×7r signaling pathway, and worked as working as C-DIM12, a NURR1 agonist. Moreover, deficiency of NURR1 in activated HSCs and Kupffer cells weakened the regulatory effect of ALB on P2×7r inhibition. NURR1-mediated inhibition of inflammatory contributed to the regulation of ALB ameliorates TAA-induced hepatic fibrosis, especially based on involving in the crosstalk of HSCs-macrophage. Therefore, ALB plays a significant part in the mitigation of TAA-induced hepatotoxicity this highlights the potential of ALB as a protective intervention for hepatic fibrosis.

Liver fibrosis is a chronic liver disease caused by prolonged liver injuries. Excessive accumulation of extracellular matrix replaces the damaged hepatocytes, leading to fibrous scar formation and fibrosis induction. Lactoferrin (LF) is a glycoprotein with a conserved, monomeric signal polypeptide chain, exhibiting diverse physiological functions, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, and antitumoral activities. Previous study has shown LF’s protective role against chemically-induced liver fibrosis in rats. However, the mechanisms of LF in liver fibrosis are still unclear. In this study, we investigated LF’s mechanisms in thioacetamide (TAA)-induced liver fibrosis in rats and TGF-β1-treated HSC-T6 cells. Using ultrasonic imaging, H&E, Masson's, and Sirius Red staining, we demonstrated LF’s ability to improve liver tissue damage and fibrosis induced by TAA. LF reduced the levels of ALT, AST, and hydroxyproline in TAA-treated liver tissues, while increasing catalase levels. Additionally, LF treatment decreased mRNA expression of inflammatory factors such as Il-1β and Icam-1, as well as fibrogenic factors including α-Sma, Collagen I, and Ctgf in TAA-treated liver tissues. Furthermore, LF reduced TAA-induced ROS production and cell death in FL83B cells, and decreased α-SMA, Collagen I, and p-Smad2/3 productions in TGF-β1-treated HSC-T6 cells. Our study highlights LF's ability to ameliorate TAA-induced hepatocyte damage, oxidative stress, and liver fibrosis in rats, potentially through its inhibitory effect on HSC activation. These findings suggest LF's potential as a therapeutic agent for protecting against liver injuries and fibrosis.

Background and purpose: Ellagic acid is a natural polyphenol compound with potential antioxidant properties that is present in most fruits, seeds, and vegetables. Therefore, this study was designed to investigate the effects of ellagic acid administration on the liver damage model caused by thioacetamide in rats. Materials and methods: In this experimental study, 60 male Wistar rats weighing approximately 200 grams were randomly divided into six groups (n=10). Liver damage was caused by a single dose (100 mg/kg) administration of thioacetamide for three consecutive days. Different doses of ellagic acid (10, 25 and 50 mg/kg) were administered to the sick mice as a single dose for three consecutive days. Finally, 24 hours after the last injection, biochemical factors (ALP, AST, ALT, LDH, bilirubin, total protein), oxidative stress markers (LPO, ROS, FRAP, GSH), ammonium ion concentration, and movement activity of the mice were examined. One-way analysis of variance and Tukey's post hoc test were used for statistical analysis. Results: Thioacetamide led to a significant increase in serum biochemical factors and oxidative stress markers in the studied groups (P

Macrophage inhibitory factor (MIF) is a multipotent cytokine, involved in the inflammatory response to infections or injuries. This study investigates the role of MIF in liver fibrosis and the modulating effect of betaine on MIF in thioacetamide (TAA)-induced liver fibrosis. The wild-type and knockout MIF−/− C57BL/6 mice were divided into the following groups: control; Bet group, which received betaine; MIF−/−; MIF−/−+Bet; TAA group, which received TAA; TAA+Bet; MIF−/−+TAA; and MIF−/−+TAA+Bet group. After eight weeks of treatment, liver tissue was collected for further analysis. The results revealed that TAA-treated MIF-deficient mice had elevated levels of hepatic TGF-β1 and PDGF-BB, as well as MMP-2, MMP-9, and TIMP-1 compared to TAA-treated wild-type mice. However, the administration of betaine to TAA-treated MIF-deficient mice reduced hepatic TGF-β1 and PDGF-BB levels and also the relative activities of MMP-2, MMP-9 and TIMP-1, albeit less effectively than in TAA-treated mice without MIF deficiency. Furthermore, the antifibrogenic effect of MIF was demonstrated by an increase in MMP2/TIMP1 and MMP9/TIMP1 ratios. The changes in the hepatic levels of fibrogenic factors were confirmed by a histological examination of liver tissue. Overall, the dual nature of MIF highlights its involvement in the progression of liver fibrosis. Its prooxidant and proinflammatory effects may exacerbate tissue damage and inflammation initially, but its antifibrogenic activity suggests a potential protective role against fibrosis development. The study showed that betaine modulates the antifibrogenic effects of MIF in TAA-induced liver fibrosis, by decreasing TGF-β1, PDGF-BB, MMP-2, MMP-9, TIMP-1, and the deposition of ECM (Coll1 and Coll3) in the liver.

This study used probiotics and micro-encapsulated clove and cinnamon oils to develop a functional cream-stuffed cake based on sweet potatoes flour and rice flour instead of wheat flour. The cake was evaluated for its physical, chemical, and sensory properties and its antioxidant capacity. The protective effect of the cake against liver injury and immunosuppression induced by thioacetamide injection in male rats was also evaluated. The study found that eugenol and cinnamaldehyde were the majority of volatile compounds in the essential oils used in the cake, with values of 78.73 % and 81.57 %, respectively, as determined by GC-MS analysis. The viable counts of added probiotics in the cake ranged from 13.15 to 11.21 log CFU/g and were still above the threshold for health benefits. The cake had an increased dietary fiber and protein content while containing a low-fat percentage compared to a commercial cake sample. The innovative cake also contained higher levels of water-soluble and fat-soluble vitamins and minerals such as iron, calcium, potassium, and zinc. The antioxidant capacity of the cake was evaluated, and it was found to contain 1827.23 mg GAE/100 g of total phenols and 97.13 mg QE/100 g of flavonoids. The cake was also found to have antioxidant activity and was effective in protecting the liver from oxidative stress and inflammation and reducing immunodeficiency associated with liver damage.

Background and purpose: Ellagic acid is a natural polyphenol compound with potential antioxidant properties that is present in most fruits, seeds, and vegetables. Therefore, this study was designed to investigate the effects of ellagic acid administration on the liver damage model caused by thioacetamide in rats. Materials and methods: In this experimental study, 60 male Wistar rats weighing approximately 200 grams were randomly divided into six groups (n=10). Liver damage was caused by a single dose (100 mg/kg) administration of thioacetamide for three consecutive days. Different doses of ellagic acid (10, 25 and 50 mg/kg) were administered to the sick mice as a single dose for three consecutive days. Finally, 24 hours after the last injection, biochemical factors (ALP, AST, ALT, LDH, bilirubin, total protein), oxidative stress markers (LPO, ROS, FRAP, GSH), ammonium ion concentration, and movement activity of the mice were examined. One-way analysis of variance and Tukey's post hoc test were used for statistical analysis. Results: Thioacetamide led to a significant increase in serum biochemical factors and oxidative stress markers in the studied groups (P<0.05). In addition, the amount of ammonium ion in the plasma, as a key effective factor in hepatic encephalopathy, was greatly increased in animals receiving thioacetamide (P<0.05). Administration of ellagic acid in different doses significantly reduced liver damage and plasma ammonium concentration (P<0.05). Conclusion: The results of this study showed that ellagic acid reduced liver damage caused by thioacetamide through its antioxidant activities. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a typical pathological state/stage involved in most chronic liver diseases and its persistence results in cirrhosis. Inflammasomes are cytoplasmic sensors that induce inflammation in response to stress. Glibenclamide (GLB) is an USFDA-approved drug for type 2 diabetes and is reported to possess anti-inflammatory activity by inhibiting inflammatory cytokines. Dimethyl fumarate (DMF) is an USFDA-approved drug for multiple sclerosis and has been reported to activate the Nrf2/ARE pathway to maintain the cellular antioxidant balance. A total of 36 rats were randomized into six groups (n = 6 each). The rats were injected with thioacetamide (TAA) 200 mg/kg, intraperitoneally every third day for eight consecutive weeks to induce liver fibrosis and oral treatment of GLB 0.5 mg/kg/day and DMF 25 mg/kg/day, and their combinations were provided for the last four consecutive weeks. Treatment with GLB, DMF, and GLB+DMF significantly protected against TAA-mediated oxidative stress and inflammatory conditions by improving hepatic function test, triglycerides, hydroxyproline, and histopathological alterations, by inhibiting the NLRP3 inflammasome signaling and fibrogenic markers, and by activating Nrf2/ARE pathway in Wistar rats. The present results suggest that simultaneous Nrf2/ARE activation and NLRP3 inflammasome inhibition could significantly contribute to developing a novel therapy for patients with liver fibrosis. [ABSTRACT FROM AUTHOR]

Acute liver injury is caused by various factors, including oxidative stress and inflammation. Coleus vettiveroides, an ayurvedic medicinal plant, is known to possess antioxidant, antibacterial, and antidiabetic properties. In this current study, we investigated the protective effect of C. vettiveroides ethanolic root extract (CVERE) against thioacetamide (TAA)‐induced acute liver injury in rats. A single dose of TAA (300 mg/kg, b.w., i.p.) was administered to induce acute liver injury. The treatment groups of rats were concurrently treated with CVERE (125 and 250 mg/kg, b.w., p.o.) and silymarin (100 mg/kg, b.w., p.o.), respectively. After 24 h of the experimental period, TAA‐induced liver injury was confirmed by increased activity of serum transaminases and malondialdehyde levels in liver tissue, decreased levels of antioxidants, upregulated expression of the inflammatory marker gene, and altered liver morphology. Whereas CVERE simultaneous treatment inhibited hepatic injury and prevented the elevation of serum aspartate and alanine transaminases, alkaline phosphatase, and lactate dehydrogenase activities. CVERE attenuated TAA‐induced oxidative stress by suppressing lipid peroxidation and restoring antioxidants such as superoxide dismutase, catalase, and reduced glutathione. Further, CVERE treatment was found to inhibit nuclear factor κB‐mediated inflammatory signaling, as indicated by downregulated pro‐inflammatory cytokines including tumor necrosis factor‐α and interleukin‐1β. Our findings suggest that CVERE prevents TAA‐induced acute liver injury by targeting oxidative stress and inflammation. Significance Statement: Coleus vettiveroides, is an herbal plant commonly used in Indian traditional medicine for a variety of ailments due to its antioxidant properties. This study provides evidence that C. vettiveroides extract is beneficial in preventing thioacetamide‐induced acute liver injury in rats due to its antioxidant potential. [ABSTRACT FROM AUTHOR]

This study was conducted to hepatoprotective effects of Coleus aromaticus aqueous leaf extract (C. aromaticus-ALE) of on Thioacetamide and Silymarin induced liver poisonousness in wistar rats. Phytochemical screenings of C. aromaticus-ALE were used to find out the preliminary constituents. Adult male wistar rats (weight range: 200-220g) were divided into 6 groups (n= 6). Thioacetamide and Silymarin stayed managed intraperitoneally arranged the 5th day to rats in all groups but the normal control. Phytochemical screen of C. aromaticus-ALE contains flavonoids, saponins, tannins, phenol, tri-terpenoids, carbohydrate, anthraquinones, and phytosteroids. The biochemical markers of hepatic damage like AST, ALT, APT, Bilirubin and cholesterol. Furthermore, a significant hepatoprotective of the aqueous extract leaf and oral dose of Thioacetamide and Silymarin. C. aromaticus-ALE did not mortality or significant changes in the body weight. Process of hepatotoxicity induced by Thioacetamide in rats was interceded by control and these effects were comparable to those administered with Silymarin. This is the first report on hepatoprotective effect of C. aromaticusALE against Thioacetamide-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]