Identification of principal cytochrome P-450 in triphenyltin metabolism in rats.
The in vivo and in vitro metabolism of triphenyltin using rat hepatic cytochrome P-450 (CYP) systems was investigated to confirm the specific CYP that is closely related to triphenyltin metabolism. No significant sex differences occurred between the in vivo and in vitro metabolic patterns of the chemical, indicating that the principal CYP for triphenyltin metabolism in rats is not a sex-specific form of CYP. In addition, seven types of complementary DNA (cDNA)-expressed rat CYPs, typical phenobarbital (PB)-inducible forms and the CYP2C subfamily were tested to determine the activity of triphenyltin metabolism. Among the CYP isoforms studied, although CYP2B1 had a small metabolic capacity, a marked dearylation of the chemical was induced by CYP2C6. Furthermore, anti-rat CYP2C6 antibodies and cimetidine, a selective CYP2C6 inhibitor, inhibited triphenyltin dearylation activity in the hepatic microsomes of rats. Taken together, these findings suggest that CYP2C6 is the principal CYP for the triphenyltin metabolism in rats.
Ohhira
Shuji
S
Department of Hygiene, Dokkyo University School of Medicine, Mibu-machi, Tochigi 321-0293, Japan. s-ohhira@dokkyomed.ac.jp
Watanabe
Masatomo
M
Matsui
Hisao
H
D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism* / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000494:pharmacology*; D000072467:Cytochrome P450 Family 2; D005260:Female; D008099:Liver; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009947:Organotin Compounds / Q000378:metabolism* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013255:Steroid 21-Hydroxylase / Q000096:biosynthesis* / Q000494:pharmacology*
D000890:Anti-Infective Agents; D009947:Organotin Compounds; D003577:Cytochrome P-450 Enzyme System; C030665:triphenyltin; C089877:Cyp2c6v1 protein, rat; D000072467:Cytochrome P450 Family 2; D013255:Steroid 21-Hydroxylase