Effects of D-003 on hepatic drug-metabolizing enzyme activities in rats.
D-003 is a mixture of very-long-chain aliphatic acids with cholesterol-lowering and concomitant anti-platelet effects. The microsomal cytochrome P-450 system comprises a superfamily of proteins present in hepatic and extrahepatic tissues that is responsible for the metabolism of many drugs. The present study was undertaken to investigate the effects of D-003 on in vivo drug-metabolizing hepatic enzymes. Two experimental series (n = 6 animals/group) were performed. In the first series rats were randomly distributed in one control and two groups treated with D-003 at 1,000 and 2,000 mg/kg for 14 days. 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 acacia gum/water vehicle. The content of microsomal P-450, b (5) 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 glutathione S-transferase were assessed. D-003 administered up to 2,000 mg/kg or 1,000 mg/kg during 14 days or 6 months did not affect the activities of the hepatic drug-metabolizing enzymes investigated. It is concluded that D-003 is not metabolized by the liver cytochrome system and that potential risk derived from drug-to-drug interactions between D-003 and concomitant drugs appears to be low.
Gámez
Rafael
R
Center of Natural Products, National Center for Scientific Research, Havana, Cuba. clinica@enet.cu
Rodeiro
Idania
I
González
Jorge
J
García
Haydee
H
D000284:Administration, Oral; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D005227:Fatty Acids / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
C418063:D-003 sugarcane wax acid mixture; D005227:Fatty Acids; D003577:Cytochrome P-450 Enzyme System