Ethionamideによる脂肪肝の発現機序に関する実験的研究(II)

Ethionamide脂肪肝における脂肪酸組成

抄録

By the oral administration of ethionamide (TH), a fatty liver is induced in rat experimentally. From the fact that glucose-6-phosphate dehydrogenase activity of the soluble fraction of liver was enhanced in TH-administered rats, it was suggested that the remarkable increase of fatty acid synthesis in liver may cause the fatty liver of TH-administered rats. In this report, the fatty acid composition of total lipid in TH-administered rat liver was analysed by means of gaschromatography, comparing with those of the control and CCI₄-administered rat livers.
Male Donryu rats weighing 100 to 150 g were used. TH (200 or 400 mg per kg body weight as a suspension in distiled water) and CCI₄ (5 ml per kg body weight as 1.1 mixture in liquid paraffin) were administered respectively by gastric tube. Rats were sacrificed at certain int erval by decapitation and livers were removed.
The extraction of total lipid of liver was done according to the method of Folch. The extracts were washed in NaC1 solution, evapolated to dryness and refluxed with H₂SO₄. methanol. The methyl esters were washed, separated, evaporated and dissolved in small amount of ethyl ether.
Gaschromatographic analysis was carried out at 180'C in a glass tube of 2, 000 mm long and 3 mm internal diameter. DEGS was used as stationary phase and nitrogen as carrier gas.
For the quantitative determination of the total fatty acid of liver, the method of Drysdale was employed.
The results obtained were as follows.
Total fatty acid increased both in the livers of TH-administered rats and in those of CCI₄administered rats. In the fatty liver induced by TH, palmitic, oleic and linoleic acids were increased and stearic and C 20 unsaturated fatty acids were decreased in the percentage of the total lipid. These changes appeared in a short period after starting the use of TH, and lasted during the period of daily administration of TH. In case of a single dose, however, these changes disappeared completely 96 hours after the administration of TH.
Increase of oleic acid and decrease of stearic acid in percentage of total lipid were also observed in the liver of CCI₄-administered rats.
From these results, especially from a d efinite increase of linoleic acid, an extrahepatic factor as well as the intrahepatic one must be discussed in regard to the origin of the accumulated fat in TH or CCI₄-administered rat liver.