Influence of mercury and cadmium intoxication on hepatic microsomal CYP2E and CYP3A subfamilies.
The effects of subchronic mercuric acetate and of acute mercuric acetate and cadmium chloride administration to rat hepatic microsomal protein and total cytochrome P450, as well as on p-nitrophenol hydroxylase (CYP2E) and erythromycin N-demethylase (CYP3A) activities were examined. It was found that Hg2+ and Cd2+ intoxication resulted in a significant decrease of total cytochrome P450 content. Acute Hg2+ and Cd2+ exposure decreased microsomal protein level. These metals also reduced CYP2E1 activity, while they did not seem to alter CYP3A1-mediated drug metabolism. This effect on CYP2E1 may be connected to free radical generation during Hg2+ and Cd2+ intoxication. Investigation is in progress using more P450 markers for elucidation of the effect of Hg2+ and Cd2+ on P450 activities.
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Greece.
A N
AN
Alexidis
E A
EA
Rekka
P N
PN
Kourounakis
D000208:Acute Disease; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002104:Cadmium / Q000633:toxicity*; D002105:Cadmium Poisoning / Q000201:enzymology; D002908:Chronic Disease; D019392:Cytochrome P-450 CYP2E1; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D008628:Mercury / Q000633:toxicity*; D008630:Mercury Poisoning / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009929:Organ Size; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D002104:Cadmium; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D008628:Mercury