Kanazawa K, Ashida H, Inoue N, Natake M
Department of Agricultural Chemistry, Kobe University, Hyogo, Japan.
J Nutr Sci Vitaminol (Tokyo). 1989 Feb;35(1):25-37. doi: 10.3177/jnsv.35.25.
In order to find the markers of the toxicity of the autoxidized lipids in the liver, rats were given a lethal amount of secondary autoxidation products of linoleic acid (400 mg/rat/day for 3 days) and then changes in the hepatic metabolic functions were analyzed. A decrease in acetyl-CoA level to half caused by the depletion of CoASH was reported in an associated paper (J. Nutr. Sci. Vitaminol., 35, 11-23, 1989). Citrate, isocitrate, and 2-oxoglutarate also decreased to half the level of those of the control group. Reduction in isocitrate dehydrogenase activity was only 25%, while NADH2 and ATP levels remained unchanged. Thus, the reduction in the citrate cycle activity was due to the decrease in acetyl-CoA. The activity of mitochondrial succinate dehydrogenase was decreased to 1/5. Other appreciable changes were depletion of glucose 6-phosphate and fructose 6-phosphate, accumulation of glucose 1-phosphate, reductions in hexokinase, phosphofructokinase, glucose-6-phosphatase, phosphoglucomutase, and phosphogluconate dehydrogenase activities, and decrease in the NADPH2 level. It was considered that these changes were caused by the depletion of glucose 6-phosphate whose synthetic pathways were abnormal. Therefore, the markers of the hepatotoxicity of secondary products were the changes in the CoASH level and the activities of succinate dehydrogenase and synthetic pathways for glucose 6-phosphate.
为了找到肝脏中自氧化脂质毒性的标志物，给大鼠喂食致死量的亚油酸二次自氧化产物（400毫克/只/天，持续3天），然后分析肝脏代谢功能的变化。在一篇相关论文（《营养科学与维生素学杂志》，35卷，11 - 23页，1989年）中报道，由于辅酶A（CoASH）的消耗，乙酰辅酶A水平降至一半。柠檬酸、异柠檬酸和2 - 氧代戊二酸也降至对照组水平的一半。异柠檬酸脱氢酶活性仅降低了25%，而还原型辅酶Ⅱ（NADH2）和三磷酸腺苷（ATP）水平保持不变。因此，柠檬酸循环活性的降低是由于乙酰辅酶A的减少。线粒体琥珀酸脱氢酶的活性降至五分之一。其他明显的变化包括6 - 磷酸葡萄糖和6 - 磷酸果糖的消耗、1 - 磷酸葡萄糖的积累、己糖激酶、磷酸果糖激酶、葡萄糖 - 6 - 磷酸酶、磷酸葡萄糖变位酶和磷酸葡萄糖酸脱氢酶活性的降低以及NADPH2水平的下降。据认为，这些变化是由合成途径异常的6 - 磷酸葡萄糖的消耗引起的。因此，二次产物肝毒性的标志物是CoASH水平的变化、琥珀酸脱氢酶的活性以及6 - 磷酸葡萄糖的合成途径。
