Effect of MG132 on proteasome activity and prooxidant/antioxidant status of rat liver subjected to ischemia/reperfusion injury

Aim: Previous studies have shown that proteasome inhibitors exerted protective effects against ischemia/reperfusion injury (IRI) of brain, heart, kidney and intestine. The aim of the present study was to investigate: (i) whether the proteasome inhibitor MG132 protects rat liver against IRI; and (ii) whether MG132 modulates prooxidant/antioxidant status of rat liver subjected to warm IRI. Methods: The left lateral and medial lobes (approximately 70% of the total liver volume) of livers of male Wistar rats were subjected to 30-min ischemia followed by 60-min reperfusion. Lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were measured in the plasma. Proteasome chymotryptic-like (ChT-L) activity, levels of thiobarbituric acid-reactive substances (TBARS), protein carbonyls (PC) and glutathione (GSH), as well as superoxidase dismutase (SOD), catalase (CAT), glutathionine peroxidase and glutathionine reductase activities were measured in liver fractions. Results: Thirty-min ischemia followed by 60-min reperfusion increased liver TBARS and PC, CAT and SOD activities, but decreased GSH level. Ischemia/reperfusion-induced oxidative stress was exacerbated in mitochondria, indicating that these organelles are the preferential target of IRI. Plasma LDH and AST levels were decreased by MG132 during both ischemia and reperfusion, while ALT values were decreased only after 30 min of reperfusion. MG132 did not significantly affect liver TBARS and GSH levels, but it increased PC and decreased ChT-L activity; the activities of CAT and SOD were also decreased. Conclusion: MG132 exerts a protective effect during the early phase of reperfusion and it modulates prooxidant/antioxidant status of rat liver subjected to warm IRI.