Effect of in vitro and in vivo treatment with mitomycin C on activities of CYP2D1/2, CYP2C11, and CYP1A2 in rat liver.
- Author:
Fu-Rong HAO
1
;
Min-Fen YAN
;
Shun-Gao TONG
;
Li-Ming XU
;
Yi-Zun JN
Author Information
- Publication Type:Journal Article
- MeSH: Alcohol Oxidoreductases; Animals; Antibiotics, Antineoplastic; pharmacology; Aryl Hydrocarbon Hydroxylases; metabolism; Biotransformation; Cytochrome P-450 CYP1A2; metabolism; Cytochrome P450 Family 2; Male; Microsomes, Liver; enzymology; Mitomycin; pharmacology; Rats; Rats, Sprague-Dawley; Steroid 16-alpha-Hydroxylase; metabolism
- From: Acta Pharmaceutica Sinica 2004;39(11):897-903
- CountryChina
- Language:English
-
Abstract:
AIMTo evaluate the effect of in vitro and in vivo treatment with mitomycin C (MMC) on activities of CYP2D1/2, CYP2C1 , and CYP1A2 in the liver of male rats.
METHODSUsing HPLC to determine the activities of the three isoenzymes in rat liver microsomes by detecting the specific metabolites of their substrates after treatment with inducers in vivo or inhibitors in vitro.
RESULTSIn vitro, MMC inhibited the activity of CYP2D1/2, CYP2C11, and CYP1A2 in dexamethasone-induced microsomes by (19 +/- 6)% (P < 0.05), (85 +/- 10)% (P < 0.01), and (36 +/- 6)% (P < 0.05), respectively, and decreased the activity of CYP1A2 in beta-naphthoflavone-induced microsomes by (58 +/- 6)% (P < 0.01). Rats were injected intraperitoneally with 20% of the LD50 of MMC for 3 or 6 d. The treatment showed no significant effect on microsomal activities of CYP2D1/2, CYP2C11 or CYP1A2.
CONCLUSIONMMC can inhibit the activities of CYP2D1/2, CYP2C11, and CYP1A2 in rat liver microsomes in vitro, but it showed no significant effect on the activities of the three isoenzymes in vivo.
