Taurine enhances the metabolism and detoxification of ethanol and prevents hepatic fibrosis in rats treated with iron and alcohol

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Abstract

The study examines the effects of taurine on the metabolism and detoxification of ethanol in liver fibrosis induced by simultaneous administration of iron carbonyl (0.5%, w/w) and ethanol (6 g/(kg day)). Ethanol and iron administration caused liver damage and fibrosis as evidenced by liver histology and biochemical profile in plasma. Over accumulation of iron and a loss in taurine in hepatic tissue was observed in fibrotic animals. The activities of alcohol dehydrogenase and aldehyde dehydrogenase were significantly reduced in these rats compared to control. Adaptive induction of activities of Cytochrome P4502E1 (CYP2E1) and aniline hydroxylase accompanied by the reduction in glutathione-S-transferase, DT-diaphorase and glyoxalases I and II was observed. Taurine administration (2% in drinking water) ameliorated the effects of ethanol and iron. Hepatic damage and fibrosis were reduced in taurine-supplemented rats. Thus taurine has the potential for the treatment of alcoholic liver fibrosis.

Introduction

Animal experiments have shown that the spectrum of alcoholic liver disease (ALD) is only partially reproduced in the intragastric rodent model of ALD and that the addition of agents like polyunsaturated fatty acid (PUFA) or iron can potentiate the effects of ethanol to produce fibrosis (Tsukamoto et al., 1995). The combination of ethanol and carbonyl iron is a well-established model of liver fibrosis and is used by several investigators (Stål and Hultcrantz, 1993, Valerio et al., 1996). Iron supplementation results in exacerbation of alcoholic liver injury by promoting reactive oxygen species (ROS) formation through Fenton or Haber–Weiss-type of reactions that convert less-reactive oxidants such as superoxide or H2O2 to more powerful oxidants such as hydroxyl radical, ferryl- or perferryl-type oxidants. ROS are documented to initiate and facilitate the fibrotic process (Pietrangeio et al.,1995).

Taurine (2-amino ethane sulfonic acid) a non-protein sulfur-containing amino acid, is the most abundant free amino acid in the body. The biological functions of taurine include bile acid conjugation, neurotransmission and reaction with certain xenobiotics (Skare et al., 1982, Emudianughe et al., 1983). In addition to these well-known functions, taurine has other important roles in membrane stabilization, calcium homeostasis, osmoregulation and cytoprotection (Huxtable, 1992). In our previous work, we observed that co-administration of taurine with ethanol-ameliorated oxidative stress, the rise in lipid levels and ATPases in liver indicating the bioprotective action of taurine in ethanol toxicity (Pushpakiran et al., 2004a, Pushpakiran et al., 2004b, Pushpakiran et al., 2005). The present study aims to investigate the effects of taurine on the metabolism and detoxification of ethanol in iron-potentiated alcoholic liver fibrosis and to study whether taurine suppresses hepatic fibrosis.

Section snippets

Chemicals

Iron carbonyl and S-d-lactoylglutathione were purchased from Sigma–Aldrich Pvt. Ltd., MO, USA. The solvents and other chemicals used were of analytical grade and purchased from Himedia Laboratories Pvt. Ltd., Mumbai, India.

Treatment of animals

Male albino rats of Wistar strain weighing 170–190 g were purchased from the Central Animal House, Rajah Muthiah Medical College, Annamalai University. The animals were housed in polypropylene cages and maintained under controlled conditions of 12 h light/12 h dark cycle and 50%

Body and liver weights

Table 1 shows the initial and final body weights, body weight gain, liver weight and liver weight/body weight ratio in experimental animals. Rats fed ethanol, ethanol plus iron gained less weight at the end of the experimental period as compared to control animals. Animals co-treated with taurine also gained weight during the experimental period. Liver weight and liver weight/body weight ratio were higher in ethanol and ethanol plus iron-treated animals compared to control. Upon treatment with

Discussion

Biochemical changes, hepatic lesions and fibrosis were observed in ethanol and ethanol plus iron-treated rats. The changes observed in ethanol plus iron group were of a greater magnitude than those observed in rats given ethanol alone.

The reduction in body weight may be related to the toxicity of the ethanol because ethanol impairs the activation and utilization of nutrients due to maldigestion or malabsorption caused by gastrointestinal disturbances (Lieber, 2000). Increased liver weight could

Conflict of interest

None.

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