Quercetin attenuated oxidative DNA damage through NRF2 signaling pathway in rats with DMH induced colon carcinogenesis.

Accumulating recent studies have demonstrated the preventive and therapeutic effects of polyphonic compounds such as quercetin in colorectal cancer. Therefore, we aimed to evaluate the underlying mechanisms for positive effects of quercetin in rats with 1,2-dimethylhydrazine (DMH)- induced colorectal cancer. For this purpose, male Wistar rats were classified as 6 groups, including group 1 without any intervention, group 2 as quercetin received rats (50 mg/kg), groups 3 as DMH received rats (20 mg/kg) group 4-6 DMH and quercetin received rats. DNA damage, DNA repair, the expression levels and activities of enzymic antioxidants, non-enzymic antioxidants, and NRF2/Keap1 signaling were evaluated in colon tissues of all groups. Our results showed significant suppression of DNA damage and induction of DNA repair in DMH + Quercetin groups, particularly in entire-period in comparison to other groups (p < .05). The expression levels and activities of enzymic and non-enzymic antioxidants were increased in DMH + Quercetin groups (p < .05). Lipid and protein peroxidation were significantly suppressed in DMH + Quercetin groups (p < .05). In addition, quercetin also modulated NRF2/Keap1 signaling and its targets, detoxifying enzymes in DMH + Quercetin groups. Our finding demonstrated that quercetin supplementation effectively reversed DMH-mediated oxidative stress and DNA damage through targeting NRF2/Keap1 signaling pathway.

Hepatoprotective effects of Shilajit on high fat-diet induced non-alcoholic fatty liver disease (NAFLD) in rats.

Background Non-alcoholic fatty liver disease (NAFLD) is the main common cause of chronic liver disease. The aim of this study is to evaluate the effect of Shilajit, a medicine of Ayurveda, on the liver damage caused by NAFLD. Materials and methods Forty male Wistar rats, after being established as fatty liver models by feeding a high-fat diet (HFD, 12 weeks), were divided randomly into five groups as follows: control (standard diet), vehicle (HFD + distilled water), high-dose Shilajit (HFD + 250 mg/kg Shilajit), low-dose Shilajit (HFD + 150 mg/kg Shilajit) and pioglitazone (HFD + 10 mg/kg pioglitazone). The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), glucose and liver glutathione peroxidase (GPx), superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, liver weight, and histopathological manifestation outcomes were measured after the 2-week intervention. Results Shilajit treatment significantly reduced the values of AST and ALT, TG, TC, LDL, glucose, liver weight, and steatosis, and instead, increased high-density lipoprotein (HDL) compared with the vehicle group (p < 0.05). Further, Shilajit treatment improved the adverse effects of HFD-induced histopathological changes in the liver as compared with the vehicle group (p < 0.001). MDA level and GPx activity increased but SOD activity decreased in the vehicle group compared with the control group (p < 0.05), while treatment with Shilajit restored the antioxidant/oxidant balance toward a significant increase in the antioxidant system in the Shilajit group (p < 0.05). Conclusions These findings suggest that Shilajit improved the histopathological NAFLD changes in the liver and indicated the potential applicability of Shilajit as a potent agent for NAFLD treatment.

Cyclophosphamide-induced testicular toxicity ameliorate by American ginseng treatment: An experimental study.

BACKGROUND: Cyclophosphamide (CP) is one of the most invasive chemotherapeutic agents, which used commonly despite of its wide spectrum toxicity. Clinical evidence showed toxic side effects of CP in multiple organ systems. OBJECTIVE: The objective of the present study was to evaluate the effects of American ginseng on CP-induced testicular toxicity in rats. MATERIALS AND METHODS: Adult male Wistar rats (220±30 gr) were randomly divided into four groups (n=7 in each). Group 1 as control received normal saline by gavage, group 2 received CP (6.1 mg/kg/day, i.p.) for a period of 50 days. Group 3 received American ginseng (500 mg/kg/day) by gavage. Group 4 received American ginseng (500 mg/kg/day) 1h prior to the administration of CP in the equal dose of group 2. The animals scarified one day after the last treatment and the effects of American ginseng on the sperm vital parameters, testicular functions, biochemical factors, and structural malformations evaluated. RESULTS: Serum testosterone concentration was significantly decreased whereas the level of malondialdehyde and DNA damage were significantly increased in animals of CP group (p<0.01). Co-administration of American ginseng reversed these parameters and improved recovery in CP+ginseng group. In addition, seminiferous tubules of testis severely damaged in the CP group but ginseng improved histologic changes in CP+ginseng group. CONCLUSION: The findings confirmed the protective effects of American ginseng on toxicity induced by CP in the reproductive system of male rats.