Vitamin E supplementation does not prevent ethanol-reduced hepatic retinoic acid levels in rats.
Chronic, excessive ethanol intake can increase retinoic acid (RA) catabolism by inducing cytochrome P450 2E1 (CYP2E1). Vitamin E (VE) is an antioxidant implicated in CYP2E1 inhibition. In the current study, we hypothesized that VE supplementation inhibits CYP2E1 and decreases RA catabolism, thereby preventing ethanol-induced hepatocyte hyperproliferation. For 1 month, 4 groups of Sprague-Dawley rats were fed a Lieber-DeCarli liquid ethanol (36% of the total energy) diet as follows: either ethanol alone (Alc group) or ethanol in combination with 0.1 mg/kg body weight of all-trans-RA (Alc + RA group), 2 mg/kg body weight of VE (Alc + VE group), or both together (Alc + RA + VE group). Control rats were pair-fed a liquid diet with an isocaloric amount of maltodextrin instead of ethanol. The ethanol-fed groups had 3-fold higher hepatic CYP2E1 levels, 50% lower hepatic RA levels, and significantly increased hepatocyte proliferation when compared with the controls. The ethanol-fed rats given VE had more than 4-fold higher hepatic VE concentrations than the ethanol-fed rats without VE, but this did not prevent ethanol induction of CYP2E1, lower hepatic retinoid levels, or hepatocellular hyperproliferation. Furthermore, VE supplementation could not prevent RA catabolism in liver microsomal fractions of the ethanol-fed rats in vitro. These results show that VE supplementation can neither inhibit ethanol-induced changes in RA catabolism nor prevent ethanol-induced hepatocyte hyperproliferation in the rat liver.
Department of Food and Nutrition and Research Institute of Science for Human Life, Kyung Hee University, Seoul 130-701, South Korea. jchung@khu.ac.kr
Jayong
J
Chung
Sudipta
S
Veeramachaneni
Chun
C
Liu
Heather
H
Mernitz
Robert M
RM
Russell
Xiang-Dong
XD
Wang
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D019587:Dietary Supplements; D000431:Ethanol / Q000009:adverse effects*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011134:Polysaccharides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014212:Tretinoin / Q000378:metabolism*; D014810:Vitamin E / Q000378:metabolism / Q000494:pharmacology*
D011134:Polysaccharides; D014810:Vitamin E; D000431:Ethanol; D014212:Tretinoin; C008315:maltodextrin; D019392:Cytochrome P-450 CYP2E1