Investigation of the protective effect of S-acetyl-glutathione in experimentally induced hepatic ischemia-reperfusion injury in rats

Hepatic ischemia-reperfusion (I/R) injury is one of the major causes of cellular damage observed during liver surgery and transplantation. Oxidative stress and inflammatory cytokines play key roles in this process. Glutathione (GSH), an endogenous antioxidant, is critically important in cellular defense mechanisms. S-acetyl-glutathione (SAG), a more stable and lipophilic derivative of GSH, is thought to provide greater intracellular penetration and stronger protective effects. This study aimed to compare the hepatoprotective effects of GSH and SAG in a rat model of hepatic I/R injury.Thirty-six adult Wistar albino rats were randomly divided into six groups: Sham, I/R control, GSH administration (0th and 24th hour), and SAG administration (0th and 24th hour) groups. Hepatic ischemia was induced by clamping the portal triad for 30 minutes, followed by 45 minutes of reperfusion. Serum biochemical parameters, tissue ELISA markers, and histopathological samples were evaluated using appropriate methods.Both GSH and SAG treatments significantly reduced serum AST, ALT, and tissue MDA, TNF-α, IL-1β, and IL-6 levels compared to the I/R control group (p < 0.05). A more pronounced decrease in IL-6 levels was observed in the SAG group, suggesting a stronger suppression of the inflammatory response. Histopathological evaluation revealed that both agents markedly decreased congestion, necrosis, and vacuolization scores, while hepatic architecture was better preserved in the SAG-treated group.In conclusion, GSH and SAG exhibited significant hepatoprotective effects against hepatic ischemia-reperfusion injury by attenuating oxidative stress and inflammation. The greater reduction of IL-6 levels in the SAG group indicates that this compound may exert a stronger anti-inflammatory effect than classical glutathione. However, further experimental and translational studies are required to elucidate the underlying biochemical mechanisms of this difference. Key Words: Hepatic ischemia-reperfusion, SAG.