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Effects of D-003 on Hepatic Drug-Metabolizing Enzyme Activities in Rats
Rafael G?ez,Idania Rodeiro,Jorge Gonzalez,Haydee Garcia 한국식품영양과학회 2004 Journal of medicinal food Vol.7 No.4
D-003 is a mixture of very-long-chain aliphatic acids with cholesterol-lowering and concomitant anti-plateleteffects. The microsomal cytochrome P-450 system comprises a superfamily of proteins present in hepatic and extrahepatictissues that is responsible for the metabolism of many drugs. The present study was undertaken to investigate the effects ofD-003 on in vivodrug-metabolizing hepatic enzymes. Two experimental series (n . 6 animals/group) were performed. In thefirst series rats were randomly distributed in one control and two groups treated with D-003 at 1,000 and 2,000 mg/kg for 14days. In the second one they were distributed in one control and three groups treated with D-003 (250, 500, and 1,000 mg/kg)for 6 months. All treatments were orally administered by gastric gavage. Control rats were orally treated only with acaciagum/water vehicle. The content of microsomal P-450, b5 cytochromes, total sulfhydryl groups, nonprotein sulfhydryl groups,and protein-bound sulfhydryl groups as well as the activities of NADPH cytochrome c reductase, aminopyrine demethylase,dimethylnitrosamine N-demethylase, 7-ethoxyresorufin O-deethylation, 7-pentoxyresorufin O-depentylation, and cytosolic glu-tathione S-transferase were assessed. D-003 administered up to 2,000 mg/kg or 1,000 mg/kg during 14 days or 6 months didnot affect the activities of the hepatic drug-metabolizing enzymes investigated. It is concluded that D-003 is not metabolizedby the liver cytochrome system and that potential risk derived from drug-to-drug interactions between D-003 and concomi-tant drugs appears to be low.