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The mechanism of inhibitory effect of cannabidiol (CBD) on the hepatic drug-metabolizing enzyme system was studied in adult male rats in vivo. Time course studies revealed that microsomal d-benzphetamine N-demethylation and testosterone 2 alpha-, 16 alpha- and 17-oxidation were markedly suppressed 6 to 48 h after the single administration of CBD (10 mg/kg, intraperitoneally). Decreases in activities of aniline hydroxylation and p-nitroanisole O-demethylation and in content of total cytochrome P450 were intermittent and moderate. On the other hand, no change was observed in reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase activity or cytochrome b5 content in the hepatic microsomes of the CBD-treated rats. Western blotting analysis showed a marked decrease in the male-specific cytochrome P450 UT-2 in the hepatic microsomes, especially 24 to 48 h after pretreatment with CBD. It is possible that CBD given 6 to 12 h before the sacrifice might interact with cytochrome P450 as a substrate, resulting in inhibition of the drug-metabolizing enzyme activities in the earlier stages. In the later stages from 24 to 48 h after CBD treatment, the reduction in content of the male-specific cytochrome P450 UT-2 may play a major role in the inhibitory effect of CBD on the hepatic drug-metabolizing enzyme system in the adult male rat in vivo.
S Narimatsu, and
K Watanabe, and
T Matsunaga, and
I Yamamoto, and
S Imaoka, and
Y Funae, and
H Yoshimura
June 2003,
Drug metabolism and disposition: the biological fate of chemicals,
S Narimatsu, and
K Watanabe, and
T Matsunaga, and
I Yamamoto, and
S Imaoka, and
Y Funae, and
H Yoshimura
December 1993,
Biochemical and biophysical research communications,
S Narimatsu, and
K Watanabe, and
T Matsunaga, and
I Yamamoto, and
S Imaoka, and
Y Funae, and
H Yoshimura
May 1992,
Biochemical pharmacology,
S Narimatsu, and
K Watanabe, and
T Matsunaga, and
I Yamamoto, and
S Imaoka, and
Y Funae, and
H Yoshimura
January 1992,
Acta physiologica Hungarica,
S Narimatsu, and
K Watanabe, and
T Matsunaga, and
I Yamamoto, and
S Imaoka, and
Y Funae, and
H Yoshimura
September 1977,
Molecular pharmacology,
S Narimatsu, and
K Watanabe, and
T Matsunaga, and
I Yamamoto, and
S Imaoka, and
Y Funae, and
H Yoshimura
March 1983,
Biochimica et biophysica acta,
S Narimatsu, and
K Watanabe, and
T Matsunaga, and
I Yamamoto, and
S Imaoka, and
Y Funae, and
H Yoshimura
July 1994,
Biochemical pharmacology,
S Narimatsu, and
K Watanabe, and
T Matsunaga, and
I Yamamoto, and
S Imaoka, and
Y Funae, and
H Yoshimura
April 1998,
Xenobiotica; the fate of foreign compounds in biological systems,
S Narimatsu, and
K Watanabe, and
T Matsunaga, and
I Yamamoto, and
S Imaoka, and
Y Funae, and
H Yoshimura
January 1994,
International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition,
S Narimatsu, and
K Watanabe, and
T Matsunaga, and
I Yamamoto, and
S Imaoka, and
Y Funae, and
H Yoshimura
March 1994,
Pharmacology,
