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GA3 is widely used as a growth stimulant in agricultural regions. The long‐term use of GA3 can cause organs damage. Chrysin is a flavonoid found in nature that is commonly used to treat organ toxicity. In this study, we examined the effect of chrysin on the testes function of GA3‐affected rats. A total of 24 male Wistar rats were divided into 4 groups. Saline was given to the control group. The chrysin group was given orally 50 mg/kg/BW of chrysin in saline. The GA3 group received a daily oral gavage of GA3 (55 mg/kg/BW). The protective group (chrysin + GA3) was given chrysin and GA3 as those described in chrysin and GA3 groups. There were an increase in MDA levels in the serum and testicular tissue of GA3‐treated group. Catalase, GSH, and SOD levels were all lowered in the GA3‐treated rats. Chrysin dramatically reduced the harmful effects of GA3 by restoring reproductive hormone levels, altered sperm parameters, and antioxidant capabilities. Furthermore, GA3 reduced the quantitative expression of steroidogenesis genes StAR and 3‐HSD, as well as Bcl2 genes, while it increased the apoptotic marker BAX; all were alleviated by the pre‐administration of chrysin. The pre‐administration of chrysin protected the GA3 group from spermatogenic vacuolation, interstitial edema, necrosis, and depletion. Chrysin inhibited oxidative stress and modulated antioxidant activity, as well as apoptosis‐/anti‐apoptosis‐related mediators in the testes. Chrysin has the potential to repair GA3‐induced testicular dysfunctions. This suggests that chrysin is preferable as a medication to mitigate GA3‐induced oxidative damage in the testes. Practical applications: Chrysin has the potential to repair GA3‐induced testicular dysfunctions. This suggests that chrysin is preferable as a medication to mitigate GA3‐induced oxidative damage in the testes. [ABSTRACT FROM AUTHOR]

The present study was conducted to test the effect of Origanum Majoranum Extract (OME) of leaves on alterations induced in a model of type 2 diabetic rats. Adult male Wistar rats were fed high fat diet for 3 weeks and injected a single dose of streptozotocin (35 mg/kg) intraperitoneally to induce type 2 diabetic rats. Diabetic rats were given aqueous extract of OME in a dose of 20 mg/kg orally for 3 weeks. Changes in lipid profiles, glucose, insulin, expression of some genes related to glucose metabolism and histopathological changes in liver and kidney were examined. Administration of OME improved and normalized dyslipidemia recorded in type 2 diabetic rats together with reduction in glucose and insulin levels. OME induced up-regulation in gene expression of glucose [adiponectin and glucose transporter-2 (GLUT-2)] and lipid metabolism [lipoprotein lipase (LPL)]. Moreover, OME normalized histopathological changes occurred in liver and kidney of diabetic rats. OME decreased lipids accumulation in liver and kidney and increased regeneration of hepatic parenchyma and restored normal renal architecture with disappearance of fat droplets. In conclusion, OME improved dyslipidemia associated with type 2 diabetes through regulation of genes related to glucose and lipid metabolism. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a serious health issue worldwide. The disease is characterized by insulin resistance (IR), which leads to dyslipidemia and alterations in the expression levels of a number of genes. Metformin is the standard treatment for T2DM; however, the exact mechanism underlying metformin regulation is not fully understood. The aim of the present study was to investigate the effects of metformin on serum lipid profiles and the expression levels of various genes that are associated with IR, as well as the histopathological changes in the liver and pancreas. A T2DM rat model was established by feeding the rats a high-fat diet for 4 weeks, combined with a dose of streptozotocin (35 mg/kg body weight). Following the successful induction of T2DM, metformin was administered orally (400 mg/kg/day) for 4 weeks. The results indicated that metformin improved the symptoms of IR by normalizing the serum lipid profiles in the diabetic rats. Furthermore, metformin upregulated the expression of insulin receptors and genes associated with lipid metabolism, including acyl-CoA oxidase, carnitine palmitoyl transferase-1 and peroxisome proliferator activated receptor-α. In addition, treatment with metformin downregulated the expression levels of fetuin-A and retinol binding protein-4 (RBP-4), while normalizing the expression of perilipin that had been reduced in the T2DM rats. Metformin administration induced regenerative changes in the hepatocyte cytoplasm and parenchyma. In the pancreas, treatment with metformin was shown to induce positive signaling for insulin and the regeneration of pancreatic β cells. In summary, metformin treatment ameliorated a number of the harmful effects associated with T2DM via the modulation of the expression levels of fetuin-A, RBP-4, perilipin and various genes associated with lipid metabolism, resulting in regenerative changes in the liver and pancreatic cells. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the molecular mechanism underlying the hepatoprotective effects of pomegranate (POM) against oxidative stress in a rat model of carbon tetrachloride (CCl4)-induced liver damage. Injection of rats with CCl4 resulted in hepatic inflammation and lipid accumulation via the upregulation of interleukin (IL)-6 and sterol regulatory element-binding protein 1c (SREBP-1c) mRNA expression. CCl4 induced downregulation of the anti-inflammatory factors alpha 2-macroglobulin (α-2M) and IL-10 in comparison with the POM treated group. In addition, CCl4 induced downregulation of superoxide dismutase (SOD), glutathione S-transferase (GST) and catalase (CAT) expression. Conversely, prior administration of POM counteracted the deleterious alterations induced by CCl4. POM downregulated CCl4-induced IL-6 upregulation, normalized the increase in SREBP-1c expression, and prevented CCl4-induced α-2M downregulation. POM counteracted CCL4-induced alterations via immunosuppressive, anti-inflammatory and regenerative effects by upregulating transforming growth factor-β1, HSP70 and IL-10 mRNA expression. In addition, POM increased reactive oxygen species scavenging activity by augmenting the antioxidant defense mechanism against CCl4 hepatotoxicity, as demonstrated by detecting SOD, CAT and GST expression. These results confirm that, at the molecular level, POM exerts hepatoprotective effects against CCl4-induced oxidative stress and liver tissue damage. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the oxidative neurotoxicity induced by silver nanoparticles (AgNPs) and assess the neuroprotective effects of quercetin against this toxicity. Forty adult male rats were divided into four equal groups: control, AgNPs (50 mg/kg intraperitoneally), quercetin (50 mg/kg orally), and quercetin + AgNPs. After 30 days, blood and brain tissue samples were collected for further studies. AgNP exposure increased lipid peroxidation and decreased glutathione peroxidase, catalase, and superoxide dismutase activities in brain tissue. AgNPs decreased serum acetylcholine esterase activity and γ-aminobutyric acid concentrations. AgNPs upregulated tumor necrosis factor-α, interleukin-1β, and Bax transcript levels. AgNPs reduced the transcripts of claudin-5, brain-derived neurotrophic factor, paraoxonase, nuclear factor-erythroid factor 2 (Nrf2), and Bcl-2. Histopathologically, AgNPs caused various degenerative changes and neuronal necrosis associated with glial cell reactions. AgNPs increased the immunohistochemical staining of glial fibrillary acidic protein (GFAP) in the cerebrum and cerebellum. Oral treatment with quercetin efficiently counteracted the opposing effects of AgNPs on brain tissue via modulation of tight junction proteins, Nrf2, and paraoxonase, and its positive mechanism in modulating pro-inflammatory cytokines and the downregulation of GFAP expression, and the apoptotic pathway. AgNPs also altered the severity of histopathological lesions and modulated GFAP immunostaining in the examined tissue. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of date palm pollen ethanolic extract (DPPE) is a conventional approach in improving the side-effects induced by Doxorubicin (DOX).DPPE mitigated DOX-induced body and heart weight changes and ameliorated DOX-induced elevated cardiac injury markers. In addition, serum cardiac troponin I concentrations (cTnI), troponin T (cTnT), and N-terminal NBP and cytosolic (Ca+2) were amplified by alleviating the inflammatory and oxidative injury markers and decreasing histopathological lesions severity. DPPE decreased DOX-induced heart injuries by mitigating inflammation, fibrosis, and apoptosis through its antioxidant effect. To reduce DOX-induced oxidative stress injuries and other detrimental effects, a combined treatment of DPPE is advocated. Doxorubicin (DOX) has a potent antineoplastic efficacy and is considered a cornerstone of chemotherapy. However, it causes several dose-dependent cardiotoxic results, which has substantially restricted its clinical application. This study was intended to explore the potential ameliorative effect of date palm pollen ethanolic extract (DPPE) against DOX-induced cardiotoxicity and the mechanisms underlying it. Forty male Wistar albino rats were equally allocated into Control (CTR), DPPE (500 mg/kg bw for 4 weeks), DOX (2.5 mg/kg bw, intraperitoneally six times over 2 weeks), and DPPE + DOX-treated groups. Pre-coadministration of DPPE with DOX partially ameliorated DOX-induced cardiotoxicity as DPPE improved DOX-induced body and heart weight changes and mitigated the elevated cardiac injury markers activities of serum aminotransferases, lactate dehydrogenase, creatine kinase, and creatine kinase-cardiac type isoenzyme. Additionally, the concentration of serum cardiac troponin I (cTnI), troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-pro BNP), and cytosolic calcium (Ca+2) were amplified. DPPE also alleviated nitrosative status (nitric oxide) in DOX-treated animals, lipid peroxidation and antioxidant molecules as glutathione content, and glutathione peroxidase, catalase, and superoxide dismutase activities and inflammatory markers levels; NF-κB p65, TNF-α, IL-1β, and IL-6. As well, it ameliorated the severity of histopathological lesions, histomorphometric alteration and improved the immune-staining of the pro-fibrotic (TGF-β1), pro-apoptotic (caspase-3 and Bax), and anti-apoptotic (Bcl-2) proteins in cardiac tissues. Collectively, pre-coadministration of DPPE partially mitigated DOX-induced cardiac injuries via its antioxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic potential. [ABSTRACT FROM AUTHOR]

Levamisole (LEVA) and garlic are prevalent immunomodulators in humans and animals. Therefore, the present study aimed to examine the immunomodulatory effects of LEVA and garlic oil (GO) alone or in combination on the immune response of Wistar rats. A total of 24 male Wistar rats were allocated into four equal groups: Control group, which was given ad libitum access to food and water; and groups 2-4, which were orally administered LEVA [2.5 mg/kg body weight (BW) every 2 days], GO, (5 ml/kg BW daily), or LEVA plus GO, respectively for 4 consecutive weeks. Serum immunoglobulin (Ig)G and IgM levels were measured using a radial immunodiffusion assay. Serum cytokine levels, including interferon (IFN)-γ, interleukin (IL)-5 and tumor necrosis factor (TNF)-α, were measured using enzyme-linked immunosorbent assay kits. Total blood counts were measured automatically using a cell counter. Serum lysozyme enzymatic activity was determined by measuring the diameters of the zones of clearance relative to lysozyme. Immunohistochemical detection of CD4 and CD8 was carried out using the streptavidin-biotinperoxidase method. Furthermore, the mRNA expression levels of IL-4, IL-5 and IL-12 were measured in the leukocytes and thymus gland by semi-quantitative polymerase chain reaction. The results revealed that LEVA increased serum levels of IFN-γ, IL-5 and TNF-α cytokines, whereas co-administration of LEVA and GO decreased the stimulatory action of LEVA alone. LEVA and GO alone increased the serum levels of IgG, IgM and total blood cell counts, and co-administration of GO and LEVA inhibited the effects of LEVA. At the cellular level, in the spleen, LEVA increased immunoreactivity of CD4 and CD8, whereas co-administration of GO with LEVA decreased this strong expression. At the molecular level, in leukocytes, LEVA upregulated the mRNA expression levels of IL-2, IL-4 and IL-5, whereas GO alone downregulated mRNA expression. Co-administration of GO with LEVA inhibited the LEVA-induced upregulation of IL-2, IL-4 and IL-5 mRNA expression. In the thymus, both LEVA and GO upregulated the mRNA expression levels of IL-4 and IL-5, whereas LEVA alone did not affect IL-12 mRNA expression. Co-administration of GO with LEVA inhibited LEVA-induced upregulation of IL-4 and GO-induced upregulation of IL-12 expression, and had an additive upregulatory effect on IL-5 expression. In conclusion, LEVA stimulated T-helper (Th)1 cytokines, whereas GO stimulated a Th2 response, and co-administration of GO with LEVA inhibited the stimulatory effects of LEVA and balanced the Th1/Th2 response. [ABSTRACT FROM AUTHOR]