Ethionamideによる脂肪肝の発現機序に関する実験的研究
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It has been reported that the hepatic functional disorders induced by pyrazinamide (PZA)or ethionamide (TH) are observed frequently, and that TH causes a fatty liver in rat experimentally. To investigate the mechanism of fatty liver formation caused by TH, the following studies were made in regard to the changes of the factor of fatty acid synthesis and of the oxidative decomposition of fatty acid in rat liver.<BR>Male Donryu rats weighing 100 to 150g w ere used. They were sacrificed at a fixed timeafter the administration of TH (60 to 200 mg/kg/day), PZA (60 to 200 mg/kg/day), CC1<SUB>4</SUB> (0.1m<I>l</I>/kg) and ethanol (5 g/kg). As regards the factors of fatty acid synthesis, the spec ific activities of glucose-6-phosphate dehydrogenase (G-6-PDH), malic enzyme (ME) and isocitrate dehydrogenase (ICDH) in the soluble fraction of liver were measured spectrophotometrically by increase of NADPH<SUB>2</SUB> at wave length 340μ p. For the study of the fatty acid oxidation, on theother hand, the respiration and oxidative phosphorylation of mitochondria isolated from liver were examined by using a polarographic oxymeter with a rotating platinum electrode. The results obtained were as follows.<BR>Fatty accumulation w a s remarkable in TH, CCl<SUB>4</SUB> or ethanol administered rat liver.<BR>Among the NADPH<SUB>2</SUB> generating enzymes examined, the activity of G-6-PDH of TH administered rat liver increased two to three fold in comparison with the control, as well as in CCl<SUB>4</SUB> administered rat liver. The activities of ME and ICDH in the liver of TH administered rat s showed no remarkable change. G-6-PDH activity was enhanced also in the liver of fastedrefed rats or in the liver of rats fed with a low protein-high carbohydrate diet.<BR>There was no greate differance in the activities of respiration or oxidative phosphorylation. between the mitochondria from TH (60 mg/kg/day for a week) administered rat liver and those from normal rat liver. But in the mitochondria from rats given 400 mg TH/kg at a. time, R. C and P: O ratios were decreased temporarily.<BR>From the results mentioned above, it is suggested that the remarkable increase of fatty acid synthesis in liver may cause the fatty liver of TH administered rats.
- 一般社団法人 日本結核病学会の論文
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