Resveratrol mitigates radiation-induced oxidative stress and tissue injury in rats: potential involvement of the Nrf2-ARE antioxidant pathway.

BACKGROUND: Ionizing radiation (IR) generates reactive oxygen species (ROS), resulting in oxidative imbalance and tissue injury. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway regulates antioxidant gene expression; however, effective radiomodulatory agents remain limited. Resveratrol (RES), a natural antioxidant with anti-inflammatory and ROS-scavenging properties, has been proposed as a potential radioprotective compound. METHODS: Forty male albino rats were randomly assigned to four groups (n = 10/group): control, RES-only (20 mg/kg/day, orally, for three weeks), irradiated, and RES-pretreated + irradiated. Fractionated whole-body gamma irradiation was delivered as 2 Gray (Gy) every other day over one week (total dose 8 Gy). Resveratrol pretreatment was administered for two weeks prior to irradiation and continued throughout the irradiation period. Hematological indices, liver function parameters, oxidative stress markers, antioxidant enzyme activities, DNA damage (comet assay), gene expression (Ho-1, Nqo1, Txnrd1, Nf-κB, Tnf-α, Bax, Caspase-3, Mapk1), and liver histopathology were evaluated 24 hours after the final irradiation session. RESULTS: IR induced significant hematological suppression, hepatocellular injury (elevated alanine aminotransferase), increased oxidative stress markers (malondialdehyde, nitric oxide, myeloperoxidase), DNA fragmentation, and altered expression of antioxidant-, inflammatory-, and apoptosis-related genes (p < .05). Resveratrol pretreatment significantly attenuated these alterations, improving hematological parameters (p = .026), reducing liver enzyme elevation, lowering oxidative stress markers, restoring antioxidant enzyme activities (p < .001), decreasing DNA damage (p < .01), and modulating expression of Nrf2-ARE-regulated antioxidant genes and inflammatory mediators (p < .01). CONCLUSIONS: These findings suggest that RES might mitigate IR-induced oxidative stress, inflammatory responses, and tissue injury in rats. The protective effects are associated with modulation of antioxidant- and inflammation-related gene expression at the transcriptional level. Further studies are warranted to confirm mechanistic involvement and evaluate translational potential.