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

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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 FeSo_4/H_2O_2 induced lipid peroxidation in the rat liver homogenates with an IC_<50> value of 30.2 μM, and protected Ac2F cell damage by t-butyl hydroperoxide in a dose-dependent manner (EC_<50> value is 2.6 μM). Also, hepatoprotective effect of Fe-TPEN (5 mg/kg, i.p.) was investigated using CCl_4 induced liver injury in rats. This complex inhibited the elevation of serum alanine aminotransferase (AST) and aspartate aminotransferase (ALT) levels in CCl_4 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 CCl_4-intoxicated rat.
公益社団法人日本薬学会の論文
1998-03-15