Effect of "Drugs for Liver Disease" on Hepatotoxic Action of Carbon Tetrachloride. IV. Relationship between Fatty Acid Composition of Phospholipids and Drug Monooxygenation Activity in Rat Liver Microsomes and Role of Phosphorylcholine

概要

論文の詳細を見る
To clarify a correlation between the fatty acid composition and the drug-metabolizing enzyme activity in liver microsomes and the action of drug for liver disease, phosphorylcholine (PC), the fatty acid composition of microsomal lipids and aminopyrine N-demethylase activity were measured during PC administration to carbon tetrachloride (CCl_4)-poisoned rats. A dose of CCl_4 for 2 days produced a clear per cent decrease in stearic and arachidonic acids and an increase of palmitic and oleic acids of microsomal phospholipids. The phosphatidylcholine in the poisoned rats consisted of less arachidonic and stearic acids and more linoleic acid. Administration of PC resulted in the restoration of the fatty acid content to the control levels at relatively early stage. It was found that there was a good correlation between the arachidonic acid content of the phospholipids, especially phosphatidylcholine, and the aminopyrine N-demethylase activity. Electron transfer between endogenous P-450 and NADPH added significantly dropped and the percentage of P-450 reduced with NADPH added was much smaller in CCl_4-poisoned rats. These results suggest that the fatty acid composition of the phospholipids may regulate the structure of the endoplasmic membrane and phospholipids of specific structure may play an essential and functional role in oxidative demethylation in the particles.
公益社団法人日本薬学会の論文
1977-01-25