Augmented resistance to oxidative stress in fatty rat livers induced by a short-term sucrose-rich diet

Hepatic steatosis and the accompanying oxidative stress have been associate d with a variety of liver diseases. It is not known if fat accumulation per se plays a direct role in the oxidative stress of the organ. This study te sted if steatosis induced by a short-term carbohydrate-rich diet results in an increased hepatic sensitivity to oxidative stress. Antioxidant status w as determined in a liver perfusion system and in isolated parenchymal, endo thelial and Kupffer cells from rats kept on sucrose-rich diet or on regular diet for 48 h. t-Butyl hydroperoxide addition (2 mM) to the perfusion flui d resulted in a release of alanine aminotransferase (ALT) in livers from co ntrols, whereas no ALT release was observed in fatty livers. After t-butyl hydroperoxide addition, oxidized glutathione release was 40% less in fatty than in control livers, whereas reduced glutathione (GSH) release was not d ifferent. Sinusoidal oxidant stress was mimicked by the addition of lipopol ysaccharide (LPS) from Escherichia coil (10 mu g/ml) followed by the additi on of opsonized zymosan (8 mg/ml) to the perfusion medium. LPS plus zymosan treatments resulted in the release of ALT in control but not in fatty live rs. At the end of perfusion, liver glutathione content was 3-fold elevated, and the tissue content of lipid peroxidation products was approx. 40% less in fatty livers compared to controls. GSH content was doubled and glucose- 6-phosphate dehydrogenase (G6PD) expression was elevated by 3- and 10-fold in sinusoidal endothelial and parenchymal cells form fatty livers compared to cells from control animals. Following H2O2 administration in vitro (0.2- 1 mM), GSH remained elevated in endothelial and parenchymal cells from fatt y livers compared to cells from controls. In contrast, G6PD activity and GS H content were similar in Kupffer cells isolated from: fatty or control liv ers. The study shows that hepatic fat accumulation caused by a short-term s ucrose diet is not accompanied by elevated hepatic lipid peroxidation, and an elevated hepatic antioxidant activity can be manifested in the presence of prominent steatosis. The diet-induced increase in G6PD expression and, t hus, the efficient maintenance of reduced glutathione in endothelial and pa renchymal cells are a supportive mechanism in the observed hepatic resistan ce against intracellular or sinusoidal oxidative stress. (C) 2000 Elsevier Science B,V. All rights reserved.