自動酸化リノール酸投与ラット肝臓の薬物代謝酵素活性に及ぼす食じビタミンＥレベルの影響

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  • Effects of Dietary Vitamin E Levels on Activities of Drug Metabolism in Rat Liver Microsomes Administered Autoxidized Linoleate

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Three groups of rats were fed on vitamin E (VE) deficient, normal (control) and rich diets for 51 days, and bloods were collected by cutting the tail ends of rats, then hemolysis (%) and serum VE content were measured. After the feeding for one more week on the same diets, autoxidized linoleate (AL) was orally administered to each rat of the three groups at a daily dose of 0.2-0.3ml/100g, continuously for five days. The blood was withdrawn from the decapitated rats, and fractions of S-9 and microsome were prepared from perfused livers. The activities and contents of enzymes in the electron tranSfer system of liver microsome, and S-9 activities were determined with hemolysis (%), serum VE content, and serum GOT and GPT activities. The hemolysis (%) and serum VE content reflected well dietary VE level before and after AL administration, respectively. AL administration increased serum GOT and GPT activities in all groups and particularly in VE deficient group. The activities of NADPH-cytochrome c reductase and the contents of cytochrome P-450 in liver microsomes remained at essentially the same level in all groups even after AL administration, except that the cytochrome P-450 content in rats given VE rich diet was higher than that of the other two groups. The S-9 activity of VE rich diet group was intact in metabolic activation of 2-acetylamino fluorene, while that of the other two groups disappeared. These results suggest that disappearance of S-9 activities in control and VE deficient diet groups was due to destruction of microsomal membrane rather than that of drug metabolic enzymes, and show that VE rich diet protects effectively the in vivo drug metabolism system under the above conditions.

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