Rutin protects t‑butyl hydroperoxide-induced oxidative impairment via modulating the Nrf2 and iNOS activity

•Rutin protects the cell morphology under oxidative stress.•Rutin suppresses oxidative stress markers and mitigates t-BHP-induced enzyme activity.•Rutin decreases the ROS generation in t-BHP-induced cell.•Rutin modulates key stress responsive genes Nrf2 and iNOS. Rutin (quercetin-3-O-rutinoside), a flavonoid, is predominantly found in the buckwheat, cranberries, mulberry and citrus fruits. It is used as a restorative in the preparation of herbal medicine, multivitamin and known to reduce the fate of heart attack. We aimed to elucidate whether rutin attenuates oxidative stress and its possible mechanism of action in ameliorating the deleterious effect of t-BHP. We also provide evidence that rutin protects the antioxidant status of erythrocytes and liver via Nrf2 and iNOS pathway from oxidative stress. Human erythrocytes and mice liver were used for the evaluation of rutin's effect against t-BHP induced oxidative stress. The non-enzymatic (GSH, MDA, -CO, –SH) and enzymatic stress markers (SOD, CAT, GPx, GR and GST) were estimated by the colorimetric method. The level of Nrf2, iNOS, liver marker enzymes, triglycerides, cholesterol, HDL-cholesterol, albumin, BUN was measured using ELISA kits. Reactive oxygen species (ROS) was quantified using flow cytometry and fluorometry. RT-PCR was used for the quantification of Nrf2 and iNOS expression levels in the liver tissue of mice. In silico studies were done through receptor-ligand binding interaction. Pre-treatment with the rutin ameliorated the toxic effect of t-BHP by modulating the basal level of GSH, -SH, MDA and –CO significantly (p