CYP2E1 and CYP3A1/2 gene expression is not associated with the ursodeoxycholate effect on ethanol-induced lipoperoxidation.
Ethanol is a well-known hepatotoxicant inducing steatosis and membrane lipoperoxidation. The aim of the present study was to investigate in rats, whether the protective effect of UDC on ethanol-induced lipid peroxidation may be related with CYP2E1 and CYP3A1/2 gene expression. We showed that UDC treatment in ethanol-fed rats induced a significant decrease in liver triglyceride concentration which was closely correlated with a reduction in malondialdehyde and hydroxyalkenal levels. In chronically ethanol-fed rats, CYP2E1 and CYP3A1/2 gene expressions were increased by a post-transcriptional mechanism. These inductions, mainly of CYP2E1, could take part in alcohol-induced hepatic lipoperoxidation. UDC modified neither the specific activity, nor the protein level, nor the mRNA level of CYP2E1 when compared with control. UDC supplementation to alcohol diet did not prevent the increase in CYP2E1 expression of ethanol-fed rats. Furthermore, CYP3A1/2 protein levels were similarly increased by ethanol and ethanol plus UDC treatment. Therefore, UDC protective effect against ethanol-induced lipoperoxidation was not associated with a modification of CYP2E1 and CYP3A1/2 expression.
Nguyen
T D
TD
Laboratory of Toxicology, School of Pharmacy, Mediterranean University, Marseilles, France.
Oliva
L
L
Villard
P H
PH
Puyoou
F
F
Sauze
C
C
Montet
A M
AM
Lacarelle
B
B
Durand
A
A
Montet
J C
JC
D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000431:Ethanol / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013250:Steroid Hydroxylases / Q000235:genetics*; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D000431:Ethanol; D014580:Ursodeoxycholic Acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D019392:Cytochrome P-450 CYP2E1; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C022657:steroid hormone 6-beta-hydroxylase