Abstract
Current study examined the boosting impacts of Withania somnifera leaf extract from Taif area (high-altitude area) against hepatic and renal toxicity induced by diclofenac in experimental rats. Withania is highly grown on Taif area as environmental herb with multiple functions. Diclofenac is non-steroidal medication used for treatment of pain but over dose has severe side effects. Thirty-two adult Wistar rats of male type were subdivided into 4 groups. The control rats (group 1) received saline. Second group received diclofenac (50 mg/kg BW intraperitoneally) at days 4 and 5. Third group received W. somnifera leaf extract (250 mg /kg body weight) for 6 days. The fourth protective group, received W. somnifera leaf extract plus diclofenac for 6 days as shown in groups 2 and 3. Diclofenac significantly increased serum AST, ALT, and decreased albumin and total proteins levels. It also increased serum concentrations of uric acid and creatinine. In addition, it increased lipid peroxidation, and decreased reduced glutathione and superoxide dismutase levels. Diclofenac increased inflammatory cytokines secretion and up-regulated hepatic oxidative stress genes (HO-1; hemoxygenase-1 and Nrf2nuclear factor erythroid 2-related factor 2 (Nrf2) and renal inflammatory transcriptional markers (TGF-β1; transforming growth factor-beta1 and COX-2; cycloxygenas-2). In parallel, hepatic caspase-3 expression was up-regulated as an apoptotic marker, while Bcl2; (B-cell lymphoma 2) mRNA expression was down regulated as anti-apoptotic marker. W. somnifera pre-administration in the protective group ameliorated the altered parameters induced by diclofenac. In conclusion, W. somnifera leaf extract has the potential to antagonize side effects of diclofenac by regulating the pathways of oxidative stress, inflammation, and apoptosis/antiapoptosis.