Murayama Hiroshi, Ikemoto Masaki, Hamaoki Masaru
Diagnostics Department, Yamasa Corp, Choshi, Chiba, Japan.
Clin Chim Acta. 2009 Mar;401(1-2):100-4. doi: 10.1016/j.cca.2008.11.027. Epub 2008 Dec 10.
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.
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.
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.
Mitochondrion-derived markers, especially OCT, appeared superior to cytosol-derived markers in the detection of alcohol-induced liver injury.
尽管线粒体衍生标志物如鸟氨酸氨甲酰基转移酶(OCT)和谷氨酸脱氢酶(GLDH)已被报道是酒精性肝损伤的良好标志物,但由于线粒体标志物不如胞质溶胶衍生标志物敏感这一观念,它们的应用受到了限制。我们确定了线粒体衍生标志物在评估酒精性肝毒性中的临床重要性。
给大鼠长期给予酒精(饮用水中含5 - 30%乙醇,有或无高脂饮食喂养15周),并通过血清OCT和GLDH以及其他肝酶如丙氨酸氨基转移酶和天冬氨酸氨基转移酶评估肝损伤。在慢性乙醇喂养模型中也评估了肝脏中这些酶的含量,以确认肝脏中酶的诱导是否反映血清活性。
长期给予乙醇后,OCT和GLDH的血清活性显著增加,而其他标志物则没有。尽管肝脏中OCT和GLDH的含量也增加了,但血清活性与肝脏活性不相关,且肝脏中增加的程度远低于血清。
在检测酒精性肝损伤方面,线粒体衍生标志物,尤其是OCT,似乎优于胞质溶胶衍生标志物。