Regulation of CYP1A1 by heavy metals and consequences for drug metabolism.
Cytochrome P450 1A1 (CYP1A1) is a hepatic and extrahepatic enzyme that is regulated by the aryl hydrocarbon receptor signaling pathway. With the growing human exposure to heavy metals, emerging evidence suggests that heavy metals exposure alter CYP1A1 enzyme activity. Heavy metals regulate CYP1A1 at different levels of its aryl hydrocarbon receptor signaling pathway in a metal- and species-dependent manner. The importance of CYP1A1 emerges from the fact that it has been always associated with the metabolism of pro-carcinogenic compounds to highly carcinogenic metabolites. However, recently CYP1A1 has gained status along with other cytochrome P450 enzymes in the metabolism of drugs and mediating drug-drug interactions. In addition, CYP1A1 has become a therapeutic tool for the bioactivation of prodrugs, particularly cytotoxic agents. In this review, we shed light on the effect of seven heavy metals, namely arsenic, mercury, lead, cadmium, chromium, copper and vanadium, on CYP1A1 and the consequences on drug metabolism.
Faculty of Pharmacy University of Alberta, 3126 Dentistry/Pharmacy Centre, Edmonton, Alberta T6G2N8, Canada.
Anwar
A
Anwar-Mohamed
Reem H
RH
Elbekai
Ayman Os
AO
El-Kadi
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D019216:Metals, Heavy / Q000494:pharmacology*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011355:Prodrugs / Q000378:metabolism; D013045:Species Specificity
D004791:Enzyme Inhibitors; D019216:Metals, Heavy; D004364:Pharmaceutical Preparations; D011355:Prodrugs; D019363:Cytochrome P-450 CYP1A1