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Liver-Type Arginase Is a Highly Sensitive Marker for Hepatocellular Damage in Rats

¹ College of Medical Technology, Kyoto University, Kyoto 606-8507, Japan

² Department of Surgery, NTT West Kyoto Hospital, Kyoto 601-8441, Japan

³ Study Center for Human Remains, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan

⁴ The National Institute of Health and Nutrition, Shinjuku-ku, Tokyo 162-8636, Japan

^aauthor for correspondence: fax 81-75-751-3945, e-mail mmas@kuhp.kyoto-u.ac.jp

Hepatic enzymes in serum, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), are routinely measured in serum for the diagnosis of hepatic disease; however, these enzymes are not liver specific because they are widely distributed in nonhepatic tissues. In contrast, urea cycle enzymes, i.e., liver-type arginase (ARG), ornithine carbamoyltransferase (OCT), and argininosuccinate synthase (AS), exist almost exclusively in the liver (1)(2)(3) and may serve as more specific markers of liver injury. It has been reported that some of the urea cycle enzymes leak rapidly from hepatocytes when liver cells are damaged (4)(5)(6)(7)(8)(9)(10)(11). Although there are several "hepatic marker" enzymes, including the urea cycle enzymes, it is not known which one of them is the most suitable enzyme for early detection of hepatocellular injury. To confirm the most suitable enzyme for this purpose, it is important to verify changes in the serum concentrations of urea cycle enzymes after liver damage, in comparison with enzymes in routine use. Two rat experimental models were designed: (a) a chemical liver injury model induced by carbon tetrachloride, and (b) an ischemia-reperfusion liver injury model. We measured the urea cycle enzymes ARG, OCT, and AS in sera, using procedures that we described previously (9)(12). Anti-OCT and AS IgGs were conjugated with N-hydroxysuccimidobiotin, essentially as described by Akhoundi et al. (13). These conjugates were used as second antibodies. Evaluation was based on the limited localization of the urea cycle enzymes in hepatocytes and the high specificity of our antibody. Serum activities of AST and ALT were measured by an . . . [Full Text of this Article]

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				B. A. Merrick, M. E. Bruno, J. H. Madenspacher, B. A. Wetmore, J. Foley, R. Pieper, M. Zhao, A. J. Makusky, A. M. McGrath, J. X. Zhou, et al. Alterations in the Rat Serum Proteome during Liver Injury from Acetaminophen Exposure J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 792 - 802. [Abstract] [Full Text] [PDF]