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

Superiority of serum type-I arginase and ornithine carbamyltransferase in the detection of toxicant-induced acute hepatic injury in rats
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DOI:
10.1016/j.cca.2008.01.023
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发表时间:
2008-05-01
影响因子:
5
通讯作者:
Nagata, Atsuo
Nagata, Atsuo
中科院分区:
医学3区
文献类型:
--
作者:
Murayama, Hiroshi;Ikemoto, Masaki;Nagata, Atsuo

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背景资料:尽管门脉周围区肝细胞的线粒体分布有限,但已提出鸟氨酸氨甲酰转移酶(OCT)是除I型谷胱甘肽转移酶(ARG)外的敏感标志物,即使在肝小叶中心损伤中也是如此。我们试图证实ARG和OCT在评价毒物引起的肝毒性方面的普遍优势,并澄清标记物的特征是否是比其定位在其临床优势中更重要的因素。方法:大鼠被给予四氯化碳、烯丙醇、D-半乳糖胺、脂多糖和刀豆球蛋白A,并通过血清ARG和OCT监测损伤过程,以及丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)。结果:ARG和OCT患者血清标志物水平的显著升高快于AST和ALT。此外,在峰值时的增加的程度总是较高的ARG和OCT比AST和ALT。结论:ARG和OCT的优越性AST和ALT在肝毒性的检测似乎是普遍的,至少在毒物引起的急性肝损伤。与细胞溶质衍生的酶ALT相比,血清中明显更快地出现源自大肠杆菌的酶OCT,这表明渗漏到循环中取决于标记物,而不是其定位。(C)2008 Elsevier B. V.保留所有权利。
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.