Strain difference (WKY, SPRD) in the hepatic antioxidant status in rat andeffect of hypertension (SHR, DOCA). Ex vivo and in vitro data

We assessed the hepatic antioxidant status of spontaneously (SHR) and desox icorticosterone acetate (DOCA)-induced hypertensive rats and that of respec tive normotensive Wistar Kyoto (WKY) and Sprague-Dawley (SPRD) rats. For th is we evaluated, ex vivo in liver cytosols, reduced glutathione (GSH) conte nt, glutathione-related enzyme (peroxidase, reductase and transferase) acti vities as well as the rate of lipid peroxidation in 9-11 week-old rats. The antioxidant status and the cytotoxicity of acetaminophen, a radical- and h ydrogen peroxide-mediated hepatotoxic compound, were also assessed in vitro in cultured hepatocytes isolated from hypertensive (SHR, DOCA) and normote nsive control (WKY, SPRD) rats. Our results suggest that a difference exist s in the hepatic antioxidant status between rat strains, with GSH levels be ing lower (-15%) and lipid peroxidation rate higher (+30%) in WKY compared to SPRD rats. In hepatocyte cultures from WKY rats, both GSH content and ca talase activity were lower (-30 and -70% respectively) compared to hepatocy te cultures from SPRD rats. This was associated with a 35% higher cytotoxic ity of acetaminophen in cultured hepatocytes from WKY rats compared to that in hepatocytes from SPRD rats. Hypertension in DOCA rats (mmHg: 221 +/- 9 vs. 138 +/- 5 in control SPRD rats) was associated with decreases (about 30 %) in both glutathione peroxidase (GSH-Px) and catalase activities, ex vivo in livers and in vitro in hepatocyte cultures. Hypertension in SHR (mmHg: 189 +/- 7 vs. 130 +/- 5 in control WKY rats) was also associated with decre ases (about 50%) in GSH-Px activity, ex vivo in livers and in vitro in hepa tocyte cultures but catalase activity was not modified. The IC50 of acetami nophen was also lower in hepatocytes from hypertensive rats compared to res pective controls, which could be related to the weakened antioxidant status in hepatocytes from hypertensive rats. Our data thus suggest that hepatocy te cultures are appropriated tools in which to assess hepatotoxicity and he patoprotection in hypertension.