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Background and purpose: Cholestasis is caused by a malfunction of the biliary liver system. Oxidative stress plays an essential role in the progression of cholestasis. This study aimed to investigate the antioxidant and hepatoprotective effects of ethanolic extract of Juniperus excelsa M. Bieb (JE) fruits on hepatic impairment induced by bile duct ligation (BDL) in rats. Experimental approach: Forty male Wistar rats were randomly divided into 4 groups; sham control + vehicle (SC), BDL + vehicle (BDL), BDL + JE extract (BDL + JE), and SC + extract (SC + JE). One day after surgery, the animals were treated with vehicle or ethanolic extract of JE (500 mg/kg/day) for 7 days. Finally, the blood was taken for biochemical and oxidative stress analysis. Furthermore, the liver tissue of rats was removed for histological examination. Findings/Results: Treatment with the extract of JE decreased the ALP level, whereas it enhanced total protein content compared to the BDL group. Also, JE increased the activity of SOD and GPx, as well as FRAP content compared to the BDL group; while it did not significantly affect the levels of MDA and inflammation markers. However, JE could not improve BDL-induced histopathological alterations in hepatic tissue. Conclusion and implication: This study demonstrated that JE may be useful as an adjuvant therapy by attenuating ALP activity, increasing serum total protein and FRAP content, as well as improving the antioxidant enzymes activity of SOD and GPx. However, further research is warranted to explore the other underlying mechanisms of action.

Plants, renowned for their rich reservoir of metabolites, play a pivotal role in addressing health-related issues. The Verbenaceae family stands out, showcasing immense potential in preventing and treating chronic diseases. Vitex trifolia L. (V. trifolia), a shrub with a rich history in traditional medicine, particularly in Eastern Asia, has garnered attention for its diverse therapeutic applications. This comprehensive review aims to bridge traditional knowledge and contemporary insights by investigating ethnopharmacology, phytochemistry, and pharmacological effects of V. trifolia. The keyword “V. trifolia” and its synonyms were searched within the main scientific databases including PubMed, Web of Science, ScienceDirect, Google Scholar, and Baidu Scholar (from 1974 to 2022, last search: 21.10.2023). Phytochemical analyses reveal a spectrum of secondary metabolites in V. trifolia, including terpenoids, flavonoids, lignans, phytosterols, anthraquinones, and fatty acids. Notably, terpenoids and flavonoids emerge as the main bioactive metabolites. Pharmacological studies validate its therapeutic potential, demonstrating significant antioxidant, anti-inflammatory, hepatoprotective, anticancer, anti-amnesic, antimicrobial, antiviral, anti-malaria, antispasmodic activities, and reported insecticidal effects. Despite existing literature exploring pharmacological attributes and secondary metabolites of related species, a conspicuous gap exists, specifically focusing on the pharmacological activities and novel methods of purification of pure metabolites from V. trifolia. This review aimed to fill this gap by delving into traditional medicinal applications, exploring secondary metabolites comprehensively, and providing an in-depth analysis of pharmacological effects of pure metabolites. Combining traditional uses with contemporary pharmacological insights, this article sought to serve as a crucial reference for future research and practical application of V. trifolia. This approach contributes substantially to understanding the plant, fostering scientific inquiry, and facilitating its broader application in healthcare.

Objectives: Liver ischemia/reperfusion damage frequently occurs in setting of hepatic resection and liver transplantation. It leads to disturbance in remote organs such as heart, lung and kidneys. This study explored the consequences of hepatic ischemia/reperfusion on the oxidative stress parameters, biochemical factors, and histopathological alterations in the kidney's rats, as well as evaluated the role of zinc sulfate on above-mentioned parameters. Materials and methods: Twenty-eight male Wistar rats were accidently assigned into four groups (n = 7). They were Sham, ischemia/reperfusion, zinc sulfate pretreatment, and zinc sulfate pretreatment + ischemia/reperfusion groups. Sham group: obtained normal saline (2 ml/day, seven consecutive days), intraperitoneally, zinc sulfate pretreatment group: obtained zinc sulfate (5 mg/kg, seven consecutive days, intraperitoneally). Ischemia/reperfusion group: obtained normal saline as mentioned previous, then rats experienced the partial ischemia (%70) for 45 min followed by 60 min reperfusion. Zinc sulfate pretreatment group: obtained zinc sulfate as mentioned previous, then rats experience the partial ischemia/reperfusion as presented earlier. At the end of investigation, blood was withdrawn, liver and renal tissues were removed. Then, biochemical and oxidative stress parameters, and histological changes were evaluated in the mentioned tissues. Results: The findings of this experiment indicated that zinc sulfate markedly reduced the serum levels of liver and kidney function tests in relative to ischemia/reperfusion group. Also, antioxidant enzymes activity, ferric reducing antioxidant power, and nitric oxide significantly increased, while malondialdehyde level declined in the renal tissue of zinc sulfate + ischemia/reperfusion group compared to ischemia/reperfusion rats. Furthermore, zinc sulfate alleviated the liver and kidneys histopathological alterations following ischemia/reperfusion. Conclusion: Zinc sulfate ameliorated liver and kidney function, and improved oxidant-antioxidant balance in favor of antioxidants. It is suggested that zinc sulfate may be beneficial effects on hepato-renal injury after ischemia/reperfusion.

Breast cancer is a challenging disease and leading cause of cancer death in women. There is no effective agent for metastatic breast cancer after surgery and chemotherapy. Alhagi maurorum (A.m) has been reported to exhibit an anticancer effect on various types of cancer cells in vitro. This study aimed to examine the suppressive effect of A.m alone and combined with docetaxel (DTX) on the breast cancer growth in mice models and the possible underlying mechanisms. In the present study, the mice were inoculated subcutaneously with the injections of 4T1 cells. Then, A.m, DTX, and their combination were administered intraperitoneally. The expressions of β-catenin (β-cat), FZD7, MMP2, HIF1-α, and VEGF A (vascular endothelial growth factor A) were investigated using RT-PCR method. Also, plasma alkaline phosphatase (ALP), alanine aminotransferase (GPT or ALT), aspartate transaminase (GOT or AST), serum creatinine, and urea were examined, and histological analyses of the tissues were conducted. The results demonstrated that A.m (500 mg/kg) combined with DTX significantly decreased the expression of β-cat, MMP2, and FZD7 as compared with the negative control group and monotherapies. Also, the mRNA levels of HIF1-α and VEGF A were suppressed significantly by DTX + A.m (500 mg/kg). Tumor weights and sizes were significantly lower and tumor inhibition rate was significantly higher in the DTX + A.m group. The A.m 500 mg/kg + DTX also suppressed the serum GPT level in tumor-bearing mice and decreased the serum urea level. Taken together, our findings suggest that DTX combined with A.m at an optimal dose of 500 mg/kg as the optimal dose can inhibit β-cat, FZD7, MMP2, and breast cancer growth via interrupting HIF-1α/VEGF signaling and might be used as a promising antiangiogenic agent for breast cancer treatment.

Asthma is an inflammatory disease of the airways. We assessed the anti-inflammatory and antioxidative impacts of quercetin, a plant derivative, on inflammatory and oxidative indices in lung tissue and serum of rats with asthma.Asth ma was induced by ovalbumin. Rats were divided into 4 groups: control, asthma+vehicle (Receieved normal saline), asthma+dexamethasone, and asthma+quercetin. After asthma induction, quercetin (50 mg/kg) and dexamethasone (2.5 mg/kg) were injected intraperitoneally once daily for 1 week. On day 50, lung histopathology indices; inflammatory factors; tissue gene expression, including GATA Binding Protein 3 (Gata-3), Tbx21 (T-bet), Transforming growth factor-β (TGF-β), Il10 (IL-10), Il1b (IL-1β), Il6 (IL-6), Acta2 (α-SMA), and Tnf (TNF-α); and oxidative stress indices (malondialdehyde [MDA], catalase [CAT], glutathione peroxidase [GPX], superoxide dismutase [SOD], and total antioxidant capacity [TAC]) in tissue and serum, were evaluated. The results showed that quercetin reduced Gata3, Tnf, Tgfb1, Il1b, and Acta2 gene expression and increased Tbx21 gene expression following asthma. Quercetin also improved oxidative stress by decreasing MDA levels and increasing TAC, CAT, SOD, and GPX levels in serum and lung tissue. Furthermore, quercetin decreased IL6 and TNFα levels and increased IL10 levels in lung tissue after asthma was treated with quercetin. Quercetin ameliorates oxidative stress and inflammation caused by asthma, especially at the tissue level. Therefore, quercetin can be considered a potent antiasthmatic agent.

Acute and chronic kidney diseases are common and are associated with the risk of kidney failure. Early detection of these disorders prevents their progression to kidney damage in later stages. The aim of this study was to investigate the prevalence of proteinuria and hematuria in a rural population in Yasuj, Iran. In this cross-sectional study, 676 people (350 females and 326 males) participated. People with positive dipstick test results entered the second screening and the urinary protein-to-creatinine ratio (UPCR) was measured. People with UPCR ≥150 mg/g were evaluated for demographic and biochemical indicators. In the initial screening, 72 subjects (10.6%) tested positive by the dipstick test with trace proteinuria or higher. The UPCR results showed that this ratio was above 150 mg/g in 42 patients (6.2%), which was approximately equivalent to more than 150 mg of protein excreted per day. There was no significant relationship between the prevalence of proteinuria and the demographic and biochemical markers. Briefly, it seems that the prevalence of proteinuria found by the dipstick test was similar to that in other parts of the world. However, according to the UPCR index, the percentage of proteinuria was significantly higher than in other studies. Because of the unknown mechanism of proteinuria, more studies based on genetic tests and kidney biopsies are needed to determine the causes of proteinuria.

Background: Toxoplasma gondii is a neuroinvasive protozoa pathogen that could manipulate its intermediate host's behavior. However, the possible link between T. gondii infection and the development of neurodegenerative disorders such as Parkinson’s disease (PD) has been proposed, we tested the hypothesis that in chronic toxoplasmosis neuroinflammation, and molecular mediators potentiate behavioral-cognitive impairments in BALB/c mice with PD. Methods: To establish chronic toxoplasmosis by Tehran strain, cysts of T. gondii were injected intraperitoneally into BALB/c mice in Kerman, Iran in 2019. To induce the PD model, mice (BALB/c) were treated with Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The behavioral experiments such as anxiety and motor coordination were performed using the Open field and Rotarod tests. Additionally, we investigated the contribution of Toxoplasma-induced neuroinflammation, and behavioral-cognitive impairments in the PD mice model. Results: Chronic toxoplasmosis caused PD-like symptoms and induced various behavioral changes in infected BALB/c mice. In T. gondii infected+MPTP treated group, T. gondii infection could potentiate PD in infected mice receiving MPTP and caused remarkable dysfunction in motor coordination and change in anxiety and depression-like behaviors similar or more severe than PD group. Conclusion: Chronic T. gondii infection exacerbates pathological progression of PD in BALB/c mice brain by promoting neuroinflammation, and behavioral changes establishing.

Introduction: Cholestasis is a disorder that the bile ducts were narrowed and bile acids are not released simply. Bile acids-induced liver damage is exacerbated by inflammation and oxidative stress. The goal of the current study was to investigate the protective impacts of fluvoxamine (Flu) on oxidant-antioxidant balance and inflammatory cytokines in the bile duct ligated (BDL) rats. Methods: Thirty-two male rats were arbitrarily allocated in 4 groups; sham-control (SC), SC+ 150 mg/kg Flu (SCF), bile duct ligation (BDL), and BDL+ 150 mg/kg Flu (BDLF). The rats received distilled water and Flu orally for one week. Biochemical analysis, hematoxylin and eosin staining, as well as oxidant/antioxidant status were evaluated. Also, the mRNA expression of TGF-β1, IL-1, TNF-α, and α-SMA were determined. Results: The findings indicated serum values of ALT, total bilirubin, and ALP slightly declined in the BDL + Flu group in contrast to BDL rats. The plasma protein carbonyl and inflammatory markers were markedly increased in the BDL group in contrast with SC group (P ≤ 0.05). Treatment with Flu in BDL rats markedly reduced the values of hepatic nitric oxide metabolite and malondialdehyde, plasma protein carbonyl, as well as TNF-α mRNA level (P ≤ 0.05). Histological parameters were improved in the BDL + Flu group in comparison to BDL merely rats. Conclusion: It seems that Flu declined oxidative stress probably by inhibiting lipid peroxidation, protein oxidation, and nitric oxide formation. Also, it reduced inflammation by decreasing TNF-α mRNA expression.

Background and purpose: Stachys pilifera is used in traditional medicine due to its antioxidant, anti-inflammatory, and antimicrobial effects. The goal of this study was to examine the renoprotective activity of the hydroalcoholic extract of aerial parts of S. pilifera on paracetamol (PCM)-induced nephrotoxicity. Experimental approach: The Wistar female rats were randomly divided into four groups including control, PCM, S. pilifera hydroalcoholic extract (SPE), and PCM + SPE. The animals received SPE (500 mg/kg) for one week and PCM (3 g/kg) on the 6th day orally. Kidney function tests and oxidant/antioxidant markers were determined in serum and tissue homogenate, respectively. Protein and mRNA levels of TNF-α, as well as hematoxylin and eosin staining, were assessed in the kidney tissue. Findings/Results: Treatment with SPE in the PCM group significantly decreased blood urea nitrogen and creatinine against the merely PCM rats (P < 0.05). The amount of nitric oxide metabolite and superoxide dismutase activity in the group receiving SPE showed a significant increase compared to PCM rats (P < 0.05). A significant difference in TNF-α levels between the groups was not observed. Histological changes were improved in the rats treated with SPE. Conclusion and implications: Totally, our findings showed that SPE can inhibit PCM nephrotoxicity by enhancing kidney function markers, antioxidant status, and histological changes. Though, more researches are required to estimate the possible mechanism of SPE.

Background and purpose: Pulmonary fibrosis is a chronic disease of the lungs caused by inflammation, species of reactive oxygen, and immune defects. Antioxidant properties of Nasturtium officinale has been reported in some studies. Therefore, the objective of the current study was to evaluate the effect of ethanolic extract of Nasturtium officinale (EENO) on bleomycin (BLM)-induced lung fibrosis in rats. Experimental approach: Forty adult male Wistar rats (180-220 g) were randomly divided into 5 experimental groups. Normal control, BLM control received a single dose of BLM (6 IU/kg) intratracheally only on the first day, EENO + BLM group received EENO (500 mg/kg) one week before intratracheal BLM instillation and two weeks afterward, BLM + EENO group and BML + vitamin E group received EENO (500 mg/kg) and vitamin E (500 mg/kg) half-hour after BLM installation, respectively. The animals were sacrificed on day 22. Change in body weight, lung index, serum level of malondialdehyde (MDA) and nitric oxide (NO) metabolite, lung tissue hydroxyproline content and lung pathology were assessed. Findings/Results: Pre- or post-treatment with EENO attenuated pulmonary fibrosis as evidenced by normalized lung index, improved histological changes and inhibited collagen deposition (hydroxyproline) in the animal lung. EENO also decreased MDA and NO metabolite release in comparison to the BLM control. vitamin E (500 mg/ kg) also significantly inhibited the BLM-induced lung toxicity. Conclusions and implications: EENO can prevent BLM-induced lung fibrosis in rats via antioxidant activities. However, more studies are needed to elicit the exact mechanism of this effect.

Background & Objective: High dose of acetaminophen (APAP) causes detrimental side effects such as hepatotoxicity. In the present study, the effects of Rosmarinic acid on oxidant-antioxidant balance in APAP-induced hepatotoxicity in male rats were investigated. Materials & Methods: A total of 18 male Wistar rats were divided into three groups: control (C), APAP (2 g / kg) and APAP + Rosmarinic acid (20 mg/kg). On the seventh day, after blood sampling, the rats were sacrificed and the number of biochemical parameters, oxidative stress markers and activity of antioxidant enzymes was measured. Statistical analysis was performed by SPSS software (V.17). Results: It was observed that the activity of alanine transaminase and aspartate transaminase enzymes significantly increased and the amount of protein carbonyl slightly increased in the APAP group compared to the control group. Glutathione peroxidase activity and total thiol levels were significantly reduced in the APAP group compared to the control group. Rosmarinic acid administration markedly reduced the activity of AST, ALT enzymes and amount of protein carbonyl compared to the APAP group while it significantly increased the activity of glutathione peroxidase and catalase enzymes. Conclusions: Rosmarinic acid reduces oxidative stress by preventing protein oxidation and increasing the activity of the antioxidant enzymes including glutathione peroxidase and catalase. The effect of hepatic protection of Rosmarinic acid may be due to its antioxidant properties and the trapping of free radicals by this compound.

Background: Compared to past decades, humans are exposed to rapidly increasing levels of radiofrequency electromagnetic radiations (RF-EMF). Despite numerous studies, the biological effects of human exposure to different levels of RF-EMF are not fully understood yet. This study aimed to evaluate the bioeffects of exposure to "900/1800 MHz" and “2.4 GHz" RF-EMFs, and x-rays alone as well as their potential interactions, i.e. inducing simple additive, adaptive, or synergistic effects. Methods: 120 Wistar rats were randomly divided into ten groups of 12 each. The rats were exposed to RF-EMF, 10 cGy, and 8 Gy x-rays, a combination of these exposures, or only sham-exposed. The levels of liver enzymes were determined in serum samples by an autoanalyzer. Moreover, the histopathological changes, and the levels of malondialdehyde (MDA), nitric oxide, ferric reducing antioxidant power, total thiols, and protein carbonyl (PCO) were measured. Results: Among the markers of liver function, gamma-glutamyltransferase was not associated with irradiation but, aspartate transaminase, alanine transaminase, and alkaline phosphatase showed some levels of association. MDA and PCO levels after 8 Gy irradiation increased, but pre-exposure to RF-EMF could modulate their changes. At the cellular level, the frequency of lobular inflammation was associated with the type of intervention. Conclusion: The exposure to both ionizing and non-ionizing radiations could alter some liver function tests. A short term pre-exposure to RF-EMF before exposure to an 8 Gy challenging dose of x-rays caused the alterations in oxidative stress markers and liver function tests, which indicate that oxidative stress is possibly involved in the adaptive response.

Oxidative stress has a major role in disease pathogenesis. However, limited studies have investigated the effect of various sample collection tubes on oxidative biomarkers. The present study aimed to evaluate the effect of different collection tubes on the variation of malondialdehyde (MDA), nitric oxide (NO), total thiol (t-SH), and ferric reducing ability of plasma (FRAP) levels. A total of 35 individuals participated in this study and each collected sample was separated into three different tubes: glass tubes (GTs), plain plastic tubes (PTs), and gel separator tubes (GSTs). The results of PTs and GSTs were compared to those of GTs as the reference tube. The comparison between the means of biomarkers in various tubes indicated that there was no significant difference in MDA results between tubes. In contrast, t-SH and NO content were significantly decreased in GSTs and PTs compared to GTs. However, the Bland-Altman analysis showed an acceptable concordance for the mentioned analytes and the statistically significant differences were not clinically significant for NO, MDA, and t-SH antioxidant parameters. Moreover, the FRAP level was considerably lower in GSTs compared to GTs. Nevertheless, the Bland-Altman analysis showed a high bias percentage for the FRAP assay when using PTs and GSTs. According to the present results, it can be concluded that switching to plastic blood collection tubes or serum separation tubes could influence the FRAP results. However, there was no interference for the interpretation of other antioxidant assays in different types of collection tubes. Hence, it is suggested to use GTs for total antioxidant capacity evaluations, especially the FRAP assay.

Herein, the effects of hydroalcoholic extracts of Thymus daenensis Celak (TDC) and Stachys pilifera Benth (SPB) plants on HepG2 cell line were investigated by using different analyses. Cytotoxicity and apoptosis of extracts were investigated by MTT method, AnnV/PI apoptosis assay, and their antioxidant capacity was evaluated by total thiol and glutathione peroxidase (GPX) assay. The results revealed that the SBP extract was more cytotoxic compared with the TDC extract and increased over time (128.49 µg/mL vs 107.11 µg/mL IC50 values for 24 and 72 h, respectively). Although, AnnV/PI apoptosis assay showed apoptosis induction for both extracts, but the caspase-3 activity assay revealed that TDC extract significantly increased caspase-3 activity compared with the control and SPB extract. Increasing the activity of GPX by SPB extract revealed that it has high antioxidant capacity. In conclusion, the TDC and SPB with high antioxidant capacity have high cytotoxicity against HepG2 cancer cells and have high capability as a medicinal plant.

Background: Pro-inflammatory cytokines are associated with systemic inflammatory responses. Objective: To investigate the levels of pro-inflammatory cytokines (IL-1b, IL-6, and TNF-a) in patients with non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) compared to healthy individuals. Methods: This case-control study was conducted on 30 patients with NAFL, 30 patients with NASH, and 30 healthy volunteers. The plasma level of IL-1b, IL-6, and TNF-a were determined by ELISA, and biochemical parameters were measured using colorimetric methods. Results: IL-1b and IL-6 levels were significantly higher in patients with NASH compared with NAFL and control group. However, TNF-a levels had no significant variations in NAFL and NASH patients compared to the control group (p=0.903 and p=0.960, respectively). Conclusion: Results showed that the levels of ALT activity and pro-inflammatory cytokines were higher in patients with NASH compared to control and NAFL subjects; Therefore, steatosis and inflammation develop as a result of excessive pro-inflammatory factors in NASH.

Introduction: Cholestasis is a liver disease caused by a malfunction of the hepato-biliary system. Oxidative stress as a systemic complication is the main characteristic of cholestasis. The aim of this study was to evaluate the anti-inflammatory and hepatoprotective effects of Portulaca oleracea (PO) methanolic extract on liver dysfunction and tissue damage induced by bile duct ligation (BDL) in rats. Materials and methods: Twenty-eight male Wistar rats were randomly divided into four groups: sham control (SC), BDL alone, SC plus 500 mg/kg methanolic extract of PO orally for 1 week, and BDL plus 500 mg/kg methanolic extract of PO orally for 1 week. After 1 week, the animals were anesthetized, and the liver and blood samples were taken from each animal. Biochemical parameters, oxidative stress biomarkers, histopathological changes, as well as the gene expression of IL-1, TNF-α, TGF-β, and α-SMA have been evaluated. Results: The methanolic extract of PO at a dose of 500 mg/kg significantly decreased the plasma levels of aminotransferases, alkaline phosphatase as compared to BDL group (P < 0.05), while it had no significant effect on the levels of oxidative stress markers in the hepatic tissue. The plasma level of malondialdehyde and ferric-reducing antioxidant power were markedly elevated in the BDL group in comparison to SC group (P < 0.05), while treatment with PO significantly reduced these markers (P < 0.05). The administration of PO attenuated hydroxyproline content, bile duct proliferation, and inflammation score in the cholestatic liver in contrast to non-treated BDL rats (P < 0.05). Moreover, the methanolic extract of PO markedly declined the expression of TNF-α and TGF-β pro inflammatory genes in contrast to BDL rats. Conclusions: Taken together, our findings showed that PO attenuated liver injury by decreasing liver function tests, inflammation, and hydroxyproline content. As a result, it is suggested that PO can be applied in cholestatic liver damage as a therapeutic or adjuvant agent.

Hypopituitarism refers to insufficient secretion of the pituitary hormones. Patients with acute adrenocorticotropic hormone (ACTH) deficiency may be presented with fatigue, dizziness, orthostatic hypotension, hypoglycemia, nausea, vomiting, or nonspecific abdominal pain. This study described an unusual case of hypopituitarism in a patient who presented with general abdominal pain, abdominal tenderness, nausea, vomiting, hypotension, and hypoglycemia. At first, the patient was admitted with the diagnosis of acute cholecystitis, but after treatment of hypopituitarism and adrenal insufficiency, his symptoms resolved completely, without the need for surgery. Hypopituitarism and secondary adrenal insufficiency should be considered in the differential diagnosis of the patients who present with acute abdomen, hypotension, or hypoglycemia.

Introduction. Chronic kidney disorder is a main public health concern. Inflammatory processes and oxidative stress are common in end-stage renal disease patients. We aimed to evaluate the effect of the hydroalcoholic extract of watercress (WC) on the inflammatory cytokines and protein carbonyl (PCO) contents in chronic hemodialysis patients. Methods. This was a double-blind randomized clinical trial performed on 46 hemodialysis patients. The participants were randomly divided into two groups: intervention group (500 mg hydroalcoholic extract of WC every day for 4 weeks) and control group (500 mg of white flour every night for 4 weeks). The blood samples were taken to determine the levels of vitamin E, PCO, and inflammatory cytokines at baseline and the end of treatment. Results. Forty-five patients completed the study (22 patients in the intervention group and 23 patients in the control group). There was a significant reduction in the PCO level (20.33 ± 4.40 vs. 15.06 ± 6.41, P=0.001) in the intervention group; also, this change was statistically significant relative to the control group. Furthermore, there were significant reductions in hs-CRP (8953.30 ± 5588.06 vs. 7249.86 ± 5091.62, P=0.007) and IL-6 (60.10 (55.99, 73.10) vs. 55.21 (53.39, 60.48), P=0.050) in the intervention group, but these changes were not significant in comparison with the control group. Conclusion. We conclude that the hydroalcoholic extract of WC reduced the PCO content in hemodialysis patients via inhibition of protein oxidation. Although WC administration had caused a significant reduction in IL-6 and CRP levels, these differences were not statistically significant relative to the control group. Further research is needed to identify the antioxidant and anti-inflammatory effects of WC in hemodialysis patients.

Vancomycin-induced nephrotoxicity (VIN) has been reported to occur in 5–35% of recipient patients. The aims of the study were to evaluate protective effects of Rosa canina (RC) on VIN in rats. Rats were randomly divided into five groups as follows: control group I, group II (received VAN 400 mg/kg/day, every 12 h at doses of 200 mg/kg/day, for 7 consecutive days), group III (VAN + RC 250 mg/kg/day, for 7 consecutive days), group IV (VAN + RC 500 mg/kg/day, for consecutive days), and group V (received RC 500 mg/kg/day, for consecutive 7 days). On the eighth day after anesthetizing the animals, blood samples were taken from the heart, and then, the kidneys were removed to investigate kidney function, oxidative stress, and histopathological marker. Also, the chemical composition of RC extract was identified by GC-MS analysis. Oral dose of 500 mg/kg RC extract significantly reduced the serum levels of blood urea nitrogen (BUN), creatinine (Cr), malondialdehyde (MDA), and nitric oxide (NO) and also the kidney tissue MDA, protein carbonyl, and NO metabolites (nitrite) levels compared to the VAN-treated group (P

Background. Renal ischemia-reperfusion (I/R) has a pivotal role in the progression of acute renal failure. Reactive oxygen species are considered the major constituents involved in the biochemical and pathophysiological changes that were shown during kidney I/R. The purpose of this study was to examine the renoprotective effects of Stachys pilifera ethanolic extract on oxidant-antioxidant status in renal I/R-injuries in male rats. Material and methods. Twenty-one male Wistar rats were arbitrarily distributed into 3 groups: sham control (SC), I/R, and I/R + Stachys pilifera ethanolic extract (500 mg/kg). The artery and vein of the right kidney were completely blocked, and the right kidney was completely removed in all groups. Then, the left kidney artery was blocked with suture thread for 30 minutes in only I/R and I/R + SP extract groups. Kidney function indices, oxidative stress markers, and hematoxylin and eosin staining were investigated in the plasma and kidney tissues. Results. It was shown that the urine Na and K, fractional excretion of Na and K, and protein carbonyl content markedly increased in the merely I/R group as compared to SC rats, while the administration of SP extract markedly reduced these indices (P

Background: Acetaminophen (APAP) is an antinociceptive and antipyretic drug that can be useful in therapeutic doses, although it can cause serious damage to the kidney if used overdose. The current study aimed to evaluate the protective effect of Thymus daenensis (TD) extract on APAP-induced kidney damage in rats. Methods: Thirty female Wistar rats were randomly divided into 5 groups: control, APAP (3 g/kg), TD (500 mg/kg), APAP + TD (500 mg/kg), and APAP + N- acetylcysteine (140 mg/kg). The APAP groups received APAP on the 6th day and the rats were sacrificed on the 7th day. Plasma levels of creatinine (Cr) and urea were measured. Ferric reducing antioxidant power (FRAP), nitric oxide (NO) metabolite, total thiol (T-SH), tumor necrosis factor-α (TNF-α) and antioxidant enzymes activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured in kidney tissue. The gene expression of TNF-α was also measured by real-time PCR. The histological examination of kidney tissue was also performed. Results: Results showed that urea, Cr and FRAP markers markedly elevated in the APAP rats compared with the control group. There was a significant decrease in T-SH levels in the APAP animals in comparison with the control group. CAT activity also augmented in the APAP group compared to the control group. Urea and Cr levels were significantly decreased in the APAP + TD group in comparison with the APAP group. The administration of TD extract significantly increased the SOD enzyme activity. Histological findings were improved in the group treated with TD extract. Conclusion: In general, the results indicate that TD extract can protect against APAP-induced nephrotoxicity by improving biochemical, histological and antioxidant effects. However, more studies are required to determine the mechanism of this extract.

The aim of the current study was to investigate the antioxidative effect of metformin (MTF) on bile duct ligation (BDL)-induced hepatic disorder and histological damage in rats. The rats were divided into 4 groups including sham control (SC), BDL alone (BDL surgery), MTF1 (BDL surgery and administration of 250 mg/kg of MFM) and MTF2 (BDL surgery and administration of 500 mg/kg of MTF). After BDL, the animals treated with MTF by gavage for 10 days. Hematoxylin and eosin staining, biochemical analysis and oxidative stress markers were assayed to determine histological alterations, liver functions, and oxidant/antioxidant status. Hepatotoxicity was verified by remarkable increase in plasma levels of aminotransferases and alkaline phosphatase activity and liver histology 10 days after the BDL surgery. Our finding showed that treatment with MTF markedly reduced plasma alkaline phosphatase and alleviated liver injury indices (P ≤ 0.05). Furthermore, BDL caused a considerable increase in the protein carbonyl and malondialdehyde content (P ≤ 0.05). However, MTF reduces oxidative stress by constraining the protein oxidation and lipid peroxidation, and increases antioxidant reserve by increasing the ferric reducing ability of plasma and reducing glutathione levels. MTF exerts antioxidative effects in the liver fibrosis and may represent a hepato-protective effect when given to rats with BDL-induced hepatic injury.

As water-soluble flavonoid derivatives, anthocyanidins and anthocyanins are the plants pigments mostly rich in berries, pomegranate, grapes, and dark color fruits. Many bioactivity properties of these advantageous phytochemicals have been reported; among them, their significant abilities in the suppression of tumor cells are of the promising therapeutic features, which have recently attracted great attention. The prostate malignancy, is considered the 2nd fatal and the most distributed cancer type in men worldwide. The present study was designated to gather the preclinical and clinical studies evaluating potencies of anthocyanidins/anthocyanins for the treatment and prevention of this cancer type for the first time. In general, findings confirm that the anthocyanins (especifically cyanidin-3-O-glucoside) indicated higher activity against prostatic neoplasms compared to their correlated anthocyanidins (e.g., delphinidin); in which potent anti-inflammatory, apoptosis, and anti-proliferative activities were analyzed. Complementary anti-prostate cancer assessment of diverse naturally occurred anthocyanidins/anthocyanins and their synthetically optimized derivatives through preclinical experiments and eventually confirmed by clinical trials can promisingly lead to discover natural-based chemotherapeutic drug options.

Chronic liver disease (CLD) affects millions of people and its impact on bone loss has become a subject of interest. Nitric oxide and endogenous opioids are suggested to increase during cholestasis/cirrhosis and may impact bone resorption by different mechanisms. The receptor activator of nuclear factor-κB (RANK)/RANK-ligand (RANKL)/osteoprotegerin (OPG) signaling pathway regulates bone resorption, but its role in metabolic bone disease subsequent to CLD is unknown. We aimed to investigate the involvement of nitrergic and opioidergic systems in bone loss relative to the RANK/RANKL/OPG pathway, in bile duct-ligated (BDL) rats. Eighty BDL/sham-operated (SO) rats received injections of 3 mg/kg/day Nω-Nitro-L-arginine methyl ester ± naltrexone (10 mg/kg/day) or saline for 28 days. Plasma bone turnover markers, OPG, RANK, and RANKL along with mRNA expression levels of the latter three were assessed. Plasma bone turnover markers and OPG level increased, but RANKL decreased in the BDL group compared with their SO controls (both: P ≤ 0.05). Administration of naltrexone reduced bone turnover markers and OPG level while increased RANKL content in comparison to BDL rats (P ≤ 0.05). As compared to untreated BDL rats, nitric oxide inhibition showed no effect on bone turnover marker i.e. OPG, RANK, and RANKL levels. BDL significantly increased RANK mRNA, but had no significant effect on RANKL and OPG mRNA expression. The lack of association between plasma levels and quantitative gene expression of RANKL and OPG suggests an indirect function of these markers in BDL rats. Considering that opioid receptor blockage by naltrexone in BDL animals caused a significant decrease in OPG and an increase in RANKL plasma contents, it could be postulated that the opioidergic system may have a regulatory effect on these bone markers.

Background: Acetaminophen (APAP) at high doses causes adverse side effects such as hepatotoxicity. The aim of the current study was to investigate the hepatoprotective and antioxidant effects of hydroalcoholic extract of Stachys pilifera. Benth (SP) on hepatotoxicity induced by APAP in male rats. Methods: Adult male Wistar rats were allocated into four groups: control (C), APAP (2 g/kg), APAP + SP (500 mg/kg), and APAP + Silymarin (SM, 100 mg/kg) as positive control group. On the seventh day, the rats were sacrificed after taking blood samples. Then levels of biochemical parameters, oxidative stress markers and activity of antioxidant enzymes were measured. Results: In the APAP group, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes activity was significantly increased and the level of protein carbonyl (PCO) was insignificantly increased as compared to control group. In addition, the activity of glutathione peroxidase (GPX) and total thiol in the APAP group was significantly decreased compared to the normal rats. Stachys pilifera. Benth extract administration significantly reduced the activity of AST and ALT enzymes and the level of PCO compared to the APAP group, while significantly elevated the activity of GPX enzyme. Conclusion: Hydroalcoholic extract of SP diminishes hepatotoxicity induced by APAP by reducing the amount of liver function indicators (AST and ALT). Furthermore, the hydroalcoholic extract of SP is capable of reducing oxidative stress through inhibiting protein oxidation as well as boosting the activity of GPX enzyme. In this respect, the hepatoprotective impact induced by the SP extract may possibly be attributable to its reactive oxygen species scavenging and antioxidant properties.

Introduction: Acetaminophen (APAP) as an analgesic and antipyretic drug can result to liver damages while using more than 4 g/day. Therefore, APAP toxicity causes the liver to dysfunction. This study aims to investigate the hepatoprotective and antioxidant activity of hydroalcoholic extract of watercress (WC) in APAP-induced hepatotoxicity in rats. Materials and methods: Randomly, twenty-four Wistar rats were divided into four groups of six each. Groups named as control, APAP, APAP + WC and APAP + S for group 1, 2, 3, and 4, respectively. Group 1 received distilled water 1 ml/kg for 7 days. In group 2, 3, and 4, rats pretreated by receiving distilled water (1 ml/kg), WC extract (500 mg/kg), silymarin extract (mg/kg) for 7 days, respectively. Of note, to induce acute hepatotoxicity in groups 2, 3, and 4, rats posttreated by orally intoxicated with single dose of APAP (2 g/kg) on the sixth day. The animals were sacrificed on the seventh day. Alanine amino transferase (ALT), aspartate amino transferase (AST), ferric reducing ability of plasma (FRAP), protein carbonyl (PCO), total thiol (T-SH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were measured in plasma. It should be noted that the chemical composition of WC extract was identified by GC-MS analysis. Results: The results have shown that there was a significant increase in AST, ALT, FRAP and PCO content in APAP group in comparison to control. Also, there was a significant reduction in T-SH levels and GPx activity in APAP group compared to control. However, administration of WC extract and silymarin not only causes a significant decrease in AST activity, but they markedly increased T-SH content and GPx activity compared to APAP group. GC-MS analysis showed the major compositions were found to be benzenepropanenitrile (48.30 %), Phytol (10.10 %), α-cadinene (9.50%) and linolenic acid (8.0). Conclusions: It is concluded that the WC extract reduces APAP-induced toxicity through its hepatoprotective and antioxidant activity in rats.

Cirrhosis is the consequence of chronic liver disease. Deleterious effects of oxidative stress on hepatocytes may be reflected in the erythrocyte membrane. Naltrexone (NTX) has been shown to attenuate hepatocellular injury in fibrotic animal models. The aim of this study was to investigate the progressive effect of CCl4 on the liver and whether the improvement of liver cirrhosis can be monitored through alterations in the erythrocyte membrane. In this study, 84 male Wistar rats were divided into 4 groups and received reagents (i.p.) as follows: 1- CCl₄, 2- NTX + CCl₄, 3- Mineral Oil (M), and 4- NTX + M. After 2, 6 and 8 weeks, the blood and liver tissue samples were collected. Plasma enzyme activities, the content of erythrocyte GSH and some membrane compositions, including protein carbonyl, protein sulfhydryl, and malondialdehyde were assessed. After 6 and 8 weeks, plasma enzyme activities and the content of protein carbonyl were higher in CCl4 group significantly, as compared to other groups (P

Several studies have shown that hepatocyte membrane composition changes in patients with cholestasis and cirrhosis. These alterations that are because of intracellular oxidative stress are supposed to be reflected in erythrocyte membrane. The aim of this study was to investigate the modification of erythrocyte membrane along with hexokinase and antioxidant enzymes during development of cirrhosis. Cirrhosis was induced by intraperitoneal injection of CCl4 in male Wistar rats. The test groups were: baseline, cholestatic, early cirrhotic and advanced cirrhotic along with an equal number of sham-control animals. The erythrocyte membrane modifications (protein sulfhydryl, protein carbonyl, and lipid peroxidation), as well as NO metabolites, were assessed. Activities of GPX, CAT, SOD and HK were also measured. Protein sulfhydryl content of the erythrocyte membrane (after 2, 6 and 10 weeks of injection) had significant progressive decrease. In contrast, protein carbonyls were remarkably increased 2 weeks after injection but significantly decreased after 6 weeks and returned to normal levels after 10 weeks. No significant difference in erythrocyte HK activity or MDA content was observed. Test groups showed significantly lower erythrocyte GPx activity after six weeks and CAT and SOD activities along with NO metabolites content after two weeks (P