Sodium Hydrosulfide Attenuates Vancomycin-Related Liver Damage in Rats: Roles of Redox Balance, Inflammation, and Cell Death

Abstract

Vancomycin (VAN), a glycopeptide antibiotic used to treat severe Gram-positive infections, may cause hepatotoxicity at high systemic exposure, limiting its clinical use. Sodium hydrosulfide (NaHS), a water-soluble hydrogen sulfide (H₂S) donor, possesses antioxidant, anti-inflammatory, anti-apoptotic, and cytoprotective properties. This study investigated the hepatoprotective effects of NaHS against VAN-induced liver injury in rats. Thirty adult male Sprague–Dawley rats were randomly assigned to five groups (n = 6): Control, NaHS (56 µmol/kg), VAN (200 mg/kg), VAN + NaHS28 (28 µmol/kg), and VAN + NaHS56 (56 µmol/kg). Hepatic injury was evaluated by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Oxidative stress was assessed by hepatic malondialdehyde (MDA), glutathione (GSH), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Inflammation, apoptosis, autophagy, and oxidative DNA damage were evaluated by measuring nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), caspase-3, beclin-1, and 8-hydroxy-2′-deoxyguanosine (8-OHdG), respectively. Histopathological examination was also performed. VAN significantly increased serum ALT and AST activities and hepatic MDA, NF-κB, TNF-α, caspase-3, beclin-1, and 8-OHdG levels, while reducing GSH content and GPx, SOD, and CAT activities (p < .001). NaHS treatment significantly attenuated these biochemical and histopathological alterations at both doses. In conclusion, NaHS protected against VAN-induced hepatotoxicity by reducing oxidative stress, inflammation, apoptosis, and oxidative DNA damage while preserving antioxidant defenses. These findings suggest that H₂S donors such as NaHS may represent promising therapeutic agents for preventing vancomycin-induced liver injury.