LAUSR

Silent information regulator 1 (SIRT‐1), a nicotinamide adenine dinucleotide‐dependent deacetylase, was found to regulate cell apoptosis, inflammation, and oxidative stress response in living organisms. Therefore, the role of SIRT‐1 in regulating forkhead box O/poly ADP‐ribose polymerase‐1 (FOXO‐1/PARP‐1) signaling could provide the necessary validation for developing new pharmacological targets for the promotion or inhibition of SIRT‐1 activity toward radiation sensitivity. In the present study, the SIRT‐1 signaling pathway is being investigated to study the possible modulatory effect of resveratrol (RSV, SIRT‐1 activator) versus nicotinamide (NAM, SIRT‐1 inhibitor) in case of liver damage induced by whole‐body gamma irradiation. Rats were exposed to 6 Gy gamma radiation after being pretreated with either RSV (10 mg/kg/day) or NAM (100 mg/kg/day) for 5 days, and subsequent examining hepatic morphological changes and apoptotic markers were assessed. The expression of SIRT‐1, FOXO‐1, and cleaved PARP‐1 in the liver was analyzed. RSV improved radiation‐induced apoptosis, mitochondrial dysfunction, and inflammation signified by low expression of caspase‐3, lactate dehydrogenase, complex‐I activity, myeloperoxidase, and total nitric oxide content. RSV increased the expression of SIRT‐1, whereas cleaved PARP‐1 and FOXO‐1 were suppressed. These protective effects were suppressed by inhibition of SIRT‐1 activity using NAM. These findings suggest that RSV can attenuate radiation‐induced hepatic injury by reducing apoptosis and inflammation via SIRT‐1 activity modulation.