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Research Library

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Mechanism for inhibitory effect of cannabidiol on microsomal testosterone oxidation in male rat liver.

  • Journal : Drug Metabolism and Disposition
  • Publication Year : 1988
  • Authors : Shizuo Narimatsu; Kazuhito Watanabe; Ikuo Yamamoto; Hidetoshi Yochimura

Effects of four cannabinoids [cannabidiol (CBD), delta 8-tetrahydrocannabinol, delta 9-tetrahydrocannabinol, and cannabinol] on hepatic microsomal oxidation of testosterone (17 beta-hydroxy-androst-4-ene-3-one) were examined in adult male rats. Only CBD (30 microM) competitively inhibited 2 alpha-hydroxy-testosterone (2 alpha-OH-T) and 16 alpha-OH-T formation by hepatic microsomes but did not affect androstenedione (androst-4-ene-3,17-dione) and 7 alpha-OH-T formation. Kinetic analyses demonstrated that the inhibitory profile of CBD for testosterone oxidation was different from those of SKF 525-A, which caused competitive inhibition for 2 alpha- and 16 alpha-hydroxylations and noncompetitive inhibition for 6 alpha-hydroxylation, and of metyrapone, which inhibited only 6 beta-hydroxylation competitively. CBD also suppressed formation of 2 alpha-OH-T, 16 alpha-OH-T, and androstenedione from testosterone, catalyzed by a reconstituted system containing hepatic cytochrome P-450 purified from phenobarbital-treated rats. Pretreatment of the rat with CBD (10 mg/kg, ip, once a day for 3 days) decreased testosterone oxidation at the 2 alpha-, 16 alpha-, and 17-positions and increased 7 alpha-OH-T formation, while total cytochrome P-450 content was decreased. These results suggest that CBD suppresses hepatic testosterone oxidation at the 2 alpha-, 16 alpha-, and 17-positions through selective inhibition of the male-specific cytochrome P-450 in the adult male rat.

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Conditions:

  • Antioxidant

Research Information:

Research Keywords:

  • Animals, Biotransformation, Cannabidiol/pharmacology, Cannabinoids/pharmacology, Cytochrome P-450, Electrophoresis, Enzyme System/metabolism, In Vitro Techniques, Inbred Strains, Liver/drug effects, Liver/enzymology, Liver/metabolism, Male, Metyrapone/pharmacology, Microsomes, Oxidation-Reduction, Polyacrylamide Gel, Pyridines/pharmacology, rats, Testosterone/metabolism

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