Marked elevation of serum mitochondrion-derived markers in mild models of non-alcoholic steatohepatitis in rats

In order to find sensitive serum markers in non-alcoholic steatohepatitis, liver-specific injury markers were thoroughly examined in mild models of NASH in rats. Wistar and Sprague-Dawley rats were fed a choline-deficient diet for 4 weeks, and serum activities of liver-specific enzyme markers were examined. In the drug-induced steatohepatitis model, tetracycline (0.4 mmol/kg) was given i.p. to rats and the course of hepatotoxicity was evaluated with serum markers, together with the accumulation of total lipid and thiobarbituric acid-reactive substances in the liver. In Wistar rats, serum activities of most enzymes tested were significantly increased. In Sprague-Dawley rats, in contrast, the serum level of ornithine carbamyltransferase and glutamate dehydrogenase were markedly elevated in the choline-deficient diet group compared with the control diet groups, whereas other markers were not significantly increased. In the tetracycline-induced steatohepatitis model, the extent of the increase was much higher in mitochondrial markers and the peak of the increase in these markers corresponded with the increase of hepatic total lipid and thiobarbituric acid-reactive substance. These observations show that serum mitochondrial enzyme markers are potent markers for non-alcoholic steatohepatitis in rats and are possibly applicable to humans.