Superiority of serum type-I arginase and ornithine carbamyltransferase in the detection of toxicant-induced acute hepatic injury in rats

Background: Despite the restricted distribution to mitochondria of hepatocytes in the periportal region, ornithine carbamyltransferase (OCT) have been suggested to be a sensitive marker in addition to type-I arginase (ARG), even in centrilobular damage of the liver. We attempted to confirm the universal advantages of ARG and OCT in the evaluation of hepatotoxicity induced by toxicants, and to clarify whether the character of a marker is a more important factor than its localization in its clinical superiority. Methods: Rats were administered carbon tetrachloride, allyl alcohol, D-galactosamine, lipopolysaccharide, and concanavalin A and the course of damage was monitored by serum ARG and OCT, together with alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Results: The significant increase in the serum levels of the markers was faster in ARG and OCT than AST and ALT. Further, the extent of the increase at the peak was always higher in ARG and OCT than in AST and ALT. Conclusion: The superiority of ARG and OCT over AST and ALT in the detection of hepatotoxicity seems universal, at least in toxicant-induced acute liver injuries. The apparent faster appearance of mitochondria-derived enzyme, OCT, in serum than cytosol-derived enzyme, ALT, shows that leakage into the circulation is dependent on the marker rather than its localization. (C) 2008 Elsevier B.V. All rights reserved.