The cytoprotective effect of α-tocopherol and daidzein against d-galactosamine–induced oxidative damage in the rat liver

Abstract

We hypothesized that the hepatotoxicity that develops after the induction of oxidative stress (induced by d-galactosamine [GalN]) can be ameliorated by α-tocopherol (ATC) and the soy isoflavone daidzein. To test this, we ranked and assigned male Wistar rats into 6 groups, which involved pretreatment (ATC or daidzein) for 1 hour followed by treatment (GalN) for 23 hours. Histopathologic analysis showed that GalN administration induced marked necrosis ( P < .001), steatosis ( P < .001), both lobular and portal inflammations ( P < .001), overall histopathologic score ( P < .001), and activation of caspase-3 in the liver ( P < .001). Immunohistochemical staining of malondialdehyde-protein adducts, a measure of oxidative stress, was increased in response to GalN ( P < .001). Paradoxically, there were increases in total ( P < .05) and cytosolic superoxide dismutase ( P < .001) activities after GalN administration, indicative of an up-regulation of antioxidant defenses. The concentration of total protein ( P < .001), albumin ( P < .01), and globulin fractions ( P < .001) in the plasma, as well as the activity of aspartate aminotransferase ( P < .001), was significantly perturbed after GalN treatment, reflective of overall acute hepatic injury. Administration of daidzein showed a significant amelioration of the Ga1N-induced increase in malondialdehyde-protein adducts ( P < .01) and cytosolic superoxide dismutase activities ( P < .01) in the liver. However, all other variables were not significantly altered in response to daidzein. In response to ATC pretreatment, the total histopathologic score ( P < .05), degree of necrosis ( P < .05), and both lobular ( P < .05) and portal ( P = .05) inflammations were significantly ameliorated. To conclude, both daidzein and ATC protect the liver against oxidative damage possibly via different pathways.