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The cytoprotective effect of alpha-tocopherol and daidzein against D-galactosamine-induced oxidative damage in the rat liver

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M C Y Wong, B Portmann, R Sherwood, O Niemela, H Koivisto, S Parkkila, K Trick, M R L'Abbe, J Wilson, P R Dash, R Snirajaskanthan, V R Preedy, H Wiseman

Original languageEnglish
Pages (from-to)865 - 875
Number of pages11
JournalMetabolism: clinical and experimental
Issue number7
PublishedJul 2007

King's Authors


We hypothesized that the hepatotoxicity that develops after the induction of oxidative stress (induced by D-galactosamine [GalN]) can be ameliorated by a-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 I hour followed by treatment (GaIN) for 23 hours. Histopathologic analysis showed that GaIN 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 malondialdehydeprotein adducts, a measure of oxidative stress, was increased in response to GaIN (P <.001). Paradoxically, there were increases in total (P <.05) and cytosolic superoxide dismutase (P <.001) activities after GaIN 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 GaIN treatment, reflective of overall acute hepatic injury. Administration of daidzein showed a significant amelioration of the GaIN-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. (c) 2007 Published by Elsevier Inc

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