Hepatoprotective Effect of Fe-TPEN on Carbon Tetrachloride Induced Liver Injury in Rats

Abstract

Fe(II)-tetrakis-N,N,N’,N'(2-pyridylmethyl) ethylenediamine (Fe-TPEN) catalyzes the dismutation of superoxide, and blocks the toxic effect of paraquat on Escherichia coli growth and survival. We examined antioxidative effects of Fe-TPEN on lipid peroxidation and t-butyl hydroperoxide induced cell damage. Fe-TPEN inhibited the FeSO4/H2O2 induced lipid peroxidation in the rat liver homogenates with an IC50 value of 30.2 μm, and protected Ac2F cell damage by t-butyl hydroperoxide in a dose-dependent manner (ECIC50 value is 2.6 μm). Also, hepatoprotective effect of Fe-TPEN (5 mg/kg, i.p.) was investigated using CC1IC4 induced liver injury in rats. This complex inhibited the elevation of serum alanine aminotransferase (AST) and aspartate aminotransferase (ALT) levels in CClIC4 induced liver injuries, and improved submassive necrosis and fatty degeneration of the hepatocytes. Fe-TPEN also prevented the loss of total and nonprotein SH contents, glutathione peroxidase and glutathione-S-transferase activity in cytosol of rat liver. Although the exact mechanism of action is not clear, antioxidative properties as well as attenuation of hepatocellular defense systems by Fe-TPEN seem to be important on its potent hepatoprotective effect in CCl4-intoxicated rat. © 1998, The Pharmaceutical Society of Japan. All rights reserved.