cell biochemistry and function Cell Biochem Funct 2001; 19: 281±285. DOI:10.1002/cbf.926 Ethanol-induced hepatotoxicity and protective effect of betaine Gu Èngo Èr Kanbak* 1 , Mine _ Inal 1 and Cengiz Bayc Ëu 2 1 Department of Biochemistry, The Medical School, Osmangazi University, Turkey 2 Department of Histology,The Medical School,Osmangazi University, Turkey The protective effects of betaine in ethanol hepatotoxicity were investigated in 24 female wistar albino rats. Animals were divided into three groups: control, ethanol and ethanol  betaine group. Animals were fed liquid diets and consumed approximately 60 diet per day. Rats were fed ethanol 8kg  1 day  1 . The ethanol  betaine group were fed ethanol plus betaine 0.5% w/v). All animal were fed for 2 months . Reduced glutathione, malondialdehyde and vitamin A were deter- mined in the liver tissue. Alanine aminotransferase activities were also measured on intracardiac blood samples. GSH levels in the ethanol group were signi®cantly lower than these in the control group  p < 0.001). GSH was elevated in the betaine group as compared to the ethanol group  p < 0.001). MDA in the ethanol group was signi®cantly higher than that in the control group  p < 0.05). MDAwas decreased in the betaine group as compared to the ethanol group  p < 0.05). Vitamin A in the ethanol group was signi®cantly lower than that in the control group  p < 0.01), but, in the ethanol  betaine group it was high compared with the ethanol group  p < 0.01). ALT in the ethanol group was higher than that in the control group  p < 0.05). Oxidative stress may play a major role in the ethanol-mediated hepatotoxicity. Betaine may protect liver against injury and it may prevent vitamin A depletion. Therefore, it may be a useful nutritional agent in the prevention of clinical problems dependent on ethanol-induced vitamin A depletion and peroxidative injury in liver. Copyright # 2001 John Wiley & Sons, Ltd. key words Ð alcohol, betaine; reduced glutathione; malondialdehyde; vitamin A; hepatotoxicity INTRODUCTION Ethanol is a direct systemic toxin that produces injury to all tissues, depending on dose and duration of expo- sure. The degree of injury varies among organ sys- tems. The liver is predominantly responsible for ethanol metabolism. 1 Aerobic organisms are able to produce reactive oxygen species ROS) such as superoxide anion, hydroxyl radical and hydrogen peroxide due to the univalent reduction of molecular oxygen. There are several antioxidant defence mechanisms which scavenge these toxic oxygen products. These mechan- isms protect cell components from radical damage. 2 Reduced glutathioneGSH) is one of the non-enzymic antioxidants. GSH has an important role in the protection of the cell from the peroxidation injury which is caused by the oxidant agents. 3 ROS lead to the peroxidation of membrane lipids and malondi- aldehyde is one of the end-products of lipid peroxi- dation. 4 Liver injury due to acute or chronic ethanol intake has been shown to be dependent on oxidative metabolism of ethanol at the cytoplasmic and/or microsomal/peroxisomal level. 5 Excessive ethanol use commonly leads to vitamin de®ciency. 1 Ethanol ingestion alters vitamin A meta- bolism. 6 Vitamin A is absorbed as retinol, which must be oxidized to retinal with the help of alcohol dehy- drogenase to be functional. Alcohol competitively inhibits the conversion of retinol to retinal in the liver. 1 It has been shown that hepatic vitamin A levels are decreased by ethanol ingestion. 7 The depletion affects hepatic cells. 8 S-adenosylmethionine SAMe) is a universal methyl donor for biological systems. Chronic ethanol Copyright # 2001 John Wiley & Sons, Ltd. Received 27 September 2000 Accepted 14 December 2000 * Correspondence to: Dr Gu Èngo Èr Kanbak, Department of Biochem- istry, The Medical School, Osmangazi University, 26480 Eskis Ë ehir, Turkey. Tel: 00 90 222 2392979. Fax: 00 90 222 2292126. E-mail: gkanbak@ogu.edu.tr Contract/grant spensor: Osmangazi University, Turkey.