Resveratrol attenuates hepatic oxidative stress and preserves gut mucosal integrity in high-fat diet-fed rats by modulating antioxidant and anti-inflammatory pathways.

This study evaluated the protective effects of resveratrol against high-fat diet (HFD)-induced hepatic dysfunction and intestinal mucus layer depletion with a focus on antioxidant and anti-inflammatory mechanisms. HFD-fed rats were treated with resveratrol for 8 weeks, and various metabolic, molecular, and histological parameters were assessed. Resveratrol therapy significantly reduced body weight gain and adiposity, lowered plasma and hepatic oxidative stress markers, and restored endogenous antioxidant enzyme activity. Liver function markers including ALT, AST, and ALP were normalized in treated animals. RT-PCR analysis showed enhanced expression of lipid-metabolizing and antioxidant genes including PPARα, CPT-1, Nrf2, and HO-1. Histological analysis revealed that resveratrol attenuated hepatic steatosis, collagen deposition, and fibrosis. Importantly, it preserved the goblet cell population within both intestinal crypts and villi, thereby maintaining the integrity of the gut-mucus barrier. These findings demonstrate that resveratrol exerts a multi-organ protective effect by simultaneously preserving intestinal mucus, improving hepatic antioxidant defenses, and reducing fibrosis. This study highlights a novel gut-liver axis mechanism for resveratrol action that extends beyond its well-known anti-obesity and mitochondrial benefits.