Structural Correlates of PPAR Agonist Rescue of Experimental Chronic Alcohol-Induced Steatohepatitis
Taurine (TAU) has protective effects on experimental liver fibrosis. The present study investigates whether benefits of TAU are mediated through attenuation of oxidative and nitrosative stresses. Liver fibrosis was induced in male Wistar rats by simultaneous administration of iron (0.5%, w/w) and ethanol (6g/kg/day) for 60 days consecutively. Significant increases in thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, protein carbonyl content and loss of non-protein, protein and total thiols were observed in the liver of iron plus alcohol-fed rats. Nitrosative stress was marked by increased levels of S-nitrosothiols and decreased nitrite content. Accumulation of nitrated and oxidatively modified proteins in liver was further evidenced by immunohistochemical localization with specific antibodies for 4-hydroxynonenol (4-HNE), 3-nitrotyrosine (3-NT) and dinitrophenol (DNP). Decrease in mitochondrial ion-transport enzymes and disturbances in calcium and iron levels were also observed in these rats. TAU administration (2% (w/v) in drinking water) significantly reduced the levels of lipid hydroperoxides, TBARS, protein carbonyl with concomitant elevation in thiol levels. The presence of 4-HNE, 3-NT and DNP-protein adducts was minimal. TAU also improved mitochondrial enzyme activities and regulated iron and calcium levels. These results show that the restorative effect of taurine in fibrosis involves amelioration of protein and lipid damage by decreasing oxidative and nitrosative stresses.