Suppression of liver microsomal drug-metabolizing enzyme activities in adult female rats pretreated with cannabidiol.
The suppression by cannabidiol (CBD) of the liver microsomal drug-metabolizing enzyme activities in female rats was demonstrated and its mechanism was examined. Pretreatment of rats with CBD (10 mg/kg, i.p.) caused temporary decreases in contents of cytochrome P450 (P450) and b5 and NADPH-cytochrome c (P450) reductase activity compared with values from the vehicle control group. p-Nitroanisole O-demethylase, aniline hydroxylase, d-benzphetamine N-demethylase and delta 9-tetrahydrocannabinol 11-hydroxylase were also decreased by the CBD pretreatment. The latter two activities took a longer time to return to control levels than the former two. However, the CBD pretreatment, which reduced the protein level of P450 UT-2 (CYP2C11) in adult male rats, did not decrease the protein level of P450 F-1 (CYP2C6) or F-2 (CYP2C12) in liver microsomes from female rats. These results suggest that the mechanisms by which CBD suppresses liver microsomal drug-metabolizing enzyme activities are different in male and female rats.
Narimatsu
S
S
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Watanabe
K
K
Matsunaga
T
T
Yamamoto
I
I
Imaoka
S
S
Funae
Y
Y
Yoshimura
H
H
D000818:Animals; D001589:Benzphetamine / Q000494:pharmacology; D002185:Cannabidiol / Q000494:pharmacology*; D013759:Dronabinol / Q000494:pharmacology; D005260:Female; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
D001589:Benzphetamine; D002185:Cannabidiol; D013759:Dronabinol; D006899:Mixed Function Oxygenases