Murayama Hiroshi, Ikemoto Masaki, Fukuda Yoshihiro, Nagata Atsuo
Diagnostics Department, YAMASA Corporation, 2-10-1 Araoi-cho, Choshi, Chiba, Japan.
Clin Chim Acta. 2008 May;391(1-2):31-5. doi: 10.1016/j.cca.2008.01.023. Epub 2008 Jan 31.
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.
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).
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.
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.
尽管鸟氨酸氨甲酰基转移酶(OCT)在肝门周区肝细胞的线粒体中分布受限,但除I型精氨酸酶(ARG)外,它也被认为是一种敏感标志物,即使在肝脏小叶中心损伤时也是如此。我们试图证实ARG和OCT在评估毒物诱导的肝毒性方面的普遍优势,并阐明标志物的特性在其临床优势中是否比其定位更重要。
给大鼠注射四氯化碳、烯丙醇、D-半乳糖胺、脂多糖和伴刀豆球蛋白A,并通过血清ARG和OCT以及丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)监测损伤过程。
ARG和OCT血清水平的显著升高比AST和ALT更快。此外,ARG和OCT在峰值时的升高幅度总是高于AST和ALT。
至少在毒物诱导急性肝损伤中,ARG和OCT在检测肝毒性方面优于AST和ALT似乎是普遍的。血清中线粒体来源的酶OCT比胞质溶胶来源的酶ALT出现得明显更快,这表明漏入循环取决于标志物而非其定位。