Ethionamideによる脂肪肝の発現機序に関する実験的研究 (IV) : Ethionamide投与ラットにおける14C-acetateの肝脂質への取り込み

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In order to clarify the mechanism of fatty liver formation by ethionamide, the effects of ethionamide on the fatty acid synthesis in rat liver were investigate. Male Donryu rats weighing 100 to 130g were used. Pure ethionamide (2-ethyl-thioisonicotinamide) suspended in distilled water was given orally through stomach tube. Rats were sacrificed within 48 hours after single administration of ethionamide, livers removed and the specific activities of NADPH2 generating enzymes in the soluble fraction of liver were measured spectrophotometrically. Another experiments were performed with regard to the incorporation of [2-14C] acetate into the liver lipids of ethionamide-administered rats. Each rat received intraperitoneally 10μCi of sodium acetate-2-14C (3.75mCiim mole) at some time after the administration of ethionamide and was sacrificed 3 hours later. Liver total lipids were extracted according to the procedure of Folch et al. Total lipids evaporated to dryness under nitrogen were dissolved in a small amount of chloroform, treated with acetone and then separated into two portions; acetone soluble and insoluble fractions. The former neutral fat fractions were evaporated to dryness and dissolved in 10ml of chloroform. The latter phospholipid fractions were dissolved in 3ml of chloroform. After evaporation of aliquots of the lipid extracts to dryness, total lipid, neutral fat and phospholipid were measured gravimetrically. Another aliquots of the lipid extracts were added 15ml of scintillation fluid and the radioactivities were assayed with a liquid scintillation spectrometer (Packard Model 3003). The results obtained were as follows. There were no remarkable changes in the NADPH2 generating enzyme activities of both 200mg and 400mg per kg body weight of ethionamide-administered rat liver. Incorporation of 14C-acetate into the total liver lipids of ethionamide-administered rats increased remarkably, and showed approximately three times the specific radioactivity of the control rat liver 3 hours after the administration of ethionamide. Furthermore, it was found that the incorporation of 14C-acetate increased particularly in the neutral fat fraction. It has been demonstrated that incorporation of 14C-palmitate into the liver lipids increased in carbon tetrachloride-administered rats, and that incorporation of 14C-acetate into the liver triglyceride increased remarkably also in orotic acid-administered rats. Other investigators suggested that the stimulation of hepatic fat synthesis might be a significant factor contributing to the development of fatty liver. Another report from this laboratory and the results presented above suggest that the utilization of acetate in the liver of ethionamide-administered rats increases and, as a result of the stimulation of fatty acid synthesis, the activity of glucose-6-phosphate dehydrogenase rises in accordance with increased requirement of NADPH2. As described in another report, however, an increased import of lipid into the liver from adipose tissue was observed in the case of a high dose administration of ethionamide. It is necessary, therefore, to investigate more minutely the relation between these factors contributing to the development of fatty liver.
日本結核病学会の論文

Ethionamideによる脂肪肝の発現機序に関する実験的研究 (IV) : Ethionamide投与ラットにおける<SUP>14</SUP>C-acetateの肝脂質への取り込み

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