Masaki Ikemoto

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.

Ornithine carbamyltransferase is a sensitive marker for alcohol-induced liver injury

BACKGROUND Although mitochondrion-derived markers such as ornithine carbamyltransferase (OCT) and glutamate dehydrogenase (GLDH) have been reported to be good markers for alcohol-induced hepatic injury, their use has been limited due to the notion that mitochondrial markers are less sensitive than cytosol-derived markers. We determined the clinical importance of mitochondrion-derived markers in the evaluation of alcohol-induced hepatotoxicity. METHODS Rats were administered alcohol chronically (5-30% ethanol in drinking water with or without high fat diet feeding for 15 weeks) and hepatic damages were evaluated by serum OCT and GLDH, together with other liver enzymes such as alanine aminotransferase and aspartate aminotransferase. Hepatic content of the enzymes was also evaluated in the chronic ethanol feeding model to confirm whether induction of the enzyme in the liver reflects the serum activity. RESULTS The serum activities of OCT and GLDH increased significantly by chronic ethanol feeding while other markers did not. Although the hepatic content of OCT and GLDH also increased, the serum activities did not correlate with the hepatic activities and the extent of increase in the liver was much less than in serum. CONCLUSIONS Mitochondrion-derived markers, especially OCT, appeared superior to cytosol-derived markers in the detection of alcohol-induced liver injury.

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

Background and Aim:  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.

A case with transient increases in serum S100A8/A9 levels implying acute inflammatory responses after pancreatic islet transplantation.

We investigated a patient with type 1 diabetes mellitus undergoing pancreatic islets transplantation. In this patient, we evaluated the clinical usefulness of serial measurement of serum S100A8/A9 complex levels for detecting acute inflammatory responses associated with rejection of transplanted pancreatic islets. The serum S100A8/A9 complex was a more sensitive marker for acute inflammation associated with islet transplant rejection than the serum C-reactive protein. Thus, the serial measurement of the serum S100A8/A9 complex concentration is useful for monitoring the patients with pancreatic islet transplantation.

Serum ornithine carbamyltransferase reflects hepatic damage in diabetic obese mice

Background and Aim:  As ornithine carbamyltransferase (OCT) has proved to be a sensitive serum marker in the detection of hepatotoxicity in several models, it is important to confirm its application to the diagnosis of non‐alcoholic fatty liver disease.