Location: Human Nutrition Research Center on Aging
Title: Vitamin E supplementation does not prevent ethanol-reduced hepatic retinoic acid levels in rats Authors
|Chung, Jayong -|
|Sudipta, Veeramachaneni -|
|Chun, Liu -|
|Russell, Robert -|
|Wang, Xiang-Dong -|
|Heather, Hernitz -|
Submitted to: Nutrition Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 12, 2009
Publication Date: October 21, 2010
Citation: Chung, J., Sudipta, V., Chun, L., Russell, R.M., Wang, X., Heather, H. 2010. Vitamin E supplementation does not prevent ethanol-reduced hepatic retinoic acid levels in rats. Nutrition Research. 29(9):664-670. Interpretive Summary: Epidemiological studies provide evidence that lycopene, a major carotenoid from tomatoes and tomato products, may act as a chemopreventive agent against certain types of cancers. We recently showed that high-fat diet induced fatty inflammation of the liver in people who do not abuse alcohol (NASH) and promoted the production of cancer in the liver in a rat model. Using this model, we investigated the efficacy of a dose of dietary lycopene from either a pure compound or a tomato extract against NASH-promoted cancer of the liver. Results showed that both lycopene and tomato extract supplementations significantly decreased the number of altered cells. These data indicate that lycopene and tomato extract can inhibit NASH-promoted liver cancer mainly as a result of reduced oxidative stress, which could be fulfilled through different mechanisms.
Technical Abstract: 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.