Hepatic blood flow and drug metabolism in glycerol-rechallenged rats

To analyze the hepatic blood flow and drug metabolism during glycerol-induced acute renal failure, 24 male Wistar rats were randomly divided into three groups: Group I received an intra-muscular injection of 1 ml/100 g body weight 50% glycerol, group II a second injection on day 14 and group III a second injection on day 42 after the first injection respectively. The inulin clearance, the aminopyrine N-demethylase activity, the NADPH-cytochrome P-450 activity and the cardiac output and blood flow to the organs were measured before and after glycerol injection. The total hepatic and renal blood flow decreased less significantly in group II compared to group I and III. Various P 450 activities were kept on a high level only in group II. This observation indicates that the maintenance not only of renal but also of hepatic blood flow plays an important role in preventing the development of glycerol-induced acute renal failure. The mechanism may be the induction of various P 450 activities resulting in an increased hepatic clearance of nephrotoxic substances.