Succinate dehydrogenase and synthetic pathways of glucose 6-phosphate are also the markers of the toxicity of orally administered secondary autoxidation products of linoleic acid in rat liver.
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.
Kanazawa
K
K
Department of Agricultural Chemistry, Kobe University, Hyogo, Japan.
Ashida
H
H
Inoue
N
N
Natake
M
M
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D005947:Glucose / Q000378:metabolism; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D008041:Linoleic Acids / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D013385:Succinate Dehydrogenase / Q000378:metabolism*
D015415:Biomarkers; D008041:Linoleic Acids; D009243:NAD; D009249:NADP; D013385:Succinate Dehydrogenase; D005952:Glucose-6-Phosphatase; D005947:Glucose