Summary We investigated the effect of betaine supplementation on ethanol induced steatosis and alterations in prooxidant and antioxidant status in the liver of guinea pigs. Animals were fed with normal chow or betaine containing chow (2% w/w) for 30 days. Ethanol (3 g/kg, i.p.) was given for the last 10 days. We found that ethanol treatment caused signif- icant increases in plasma transaminase activities, hepatic triglyceride and lipid peroxide levels. Significant decreases in glutathione (GSH), α-tocopherol and total ascorbic acid (AA) levels were also observed, but hepatic superoxide dis- mutase, glutathione peroxidase and glutathione transferase activities remained unchanged as compared with those in controls. Betaine treatment together with ethanol in guinea pigs is found to decrease hepatic triglyceride, lipid perox- ide levels and serum transaminase activities and to increase GSH levels. No changes in α-tocopherol and total AA lev- els and antioxidant enzyme activities were observed with betaine treatment in alcohol treated guinea pigs. In addi- tion, histopathological assessment of guinea pigs showed that betaine reduced the alcoholic fat accumulation in the liver. Based on these data, betaine treatment has a restoring effect on the alterations in triglyceride, lipid peroxide and GSH levels following ethanol ingestion. Introduction Oxidative stress is known to play an important role in the pathogenesis of ethanol-induced liver injury. The ox- Exp Toxic Pathol 2004; 55: 505–509 http://www.elsevier.de/etp 0940-2993/04/55/06-505 $ 30.00/0 505 Departments of 1 Biochemistry and 3 Pathology, I ˙ stanbul Faculty of Medicine, I ˙ stanbul University, 2 The Experimental and Medical Research Center, I ˙ stanbul University, I ˙ stanbul, Turkey The effect of betaine treatment on triglyceride levels and oxidative stress in the liver of ethanol-treated guinea pigs JALE BALKAN 1 ,SERDAR ÖZTEZCAN 1 , MUTLU KÜÇÜK 2 , UG ˇUR ÇEVI ˙ KBAS ¸ 3 , NECLA KOÇAK-TOKER 1 , and MÜJDAT UYSAL 1 With one figure and one table Received: December 29, 2003; Revised: March 29, 2004; Accepted: April 7, 2004 Address for correspondence: Dr. med MÜJDAT UYSAL, Department of Biochemistry, I ˙ stanbul Faculty of Medicine, I ˙ stanbul University, 34093 Çapa-I ˙ stanbul, Turkey; Tel.: +90 212 414 21 88; Fax: + 90 212 635 11 61; E-mail: mujdatuysal@hotmail.com Key words: betaine; ethanol; steatosis; oxidative stress; guinea pigs. Abbreviations: AA: ascorbic acid; ALT: alanine transaminase; AST: aspartate transaminase; BHMT: betaine-homocys- teine methyltransferase; DC: diene conjugate; GSH: glutathione; GSH-Px: glutathione peroxidase; GST: glutathione transferase; HC: homocysteine; MDA: malondialdehyde; SAM: S-adenosyl methionine; SOD: superoxide dismutase. idative stress induced by ethanol is a result of the pro- duction of free radical species during several stages of ethanol metabolism (NORDMANN et al. 1992; ISHII et al. 1997) Several experimental (NORDMANN et al. 1992; ISHII et al. 1997; BAILEY et al. 2001; BALKAN et al. 2002) and clinical (ALEYNIK et al. 1998; MUTLU-TÜRKOG ˇ LU et al. 2000) studies have shown that ethanol ingestion al- ters the prooxidant-antioxidant balance in the organism. Another characteristic change related to alcohol metabolism is altered sulfur amino acid metabolism, in- cluding decreased conversion of methionine to S-adeno- sylmethionine (SAM) and homocysteine (HC) to methio- nine (BARAK et al. 2001; ALEYNIK and LIEBER 2000). Ethanol ingestion is found to result in decreases in SAM levels and increases in HC levels (BARAK et al. 1996; ALEYNIK and LIEBER 2000). Important transmethylation and transsulfuration pathways can be impaired by SAM deficiency and this may lead to liver injury. According to clinical (LIEBER 1999; MATO et al. 1999) and experimen- tal (MURIEL and MOURELLE 1992; GASSO et al. 1996; JUN- NILA 1998; DEULOFEU et al. 2000; MONTILLA-LOPEZ et al. 2000) findings, it has been accepted that SAM treatment has hepatoprotective effects. Although the mechanisms underlying this hepatoprotective effect are not complete- ly known, effects such as restorating hepatocyte mem- branes (MURIEL and MOURELLE 1992),enhancing antioxi- dant reserve, especially glutathione levels and decreasing lipid peroxide levels (GASSO et al. 1996; DEULOFEU et al. 2000; MONTILLA- LOPEZ et al. 2000) are suggested.