The cytoprotective effect of alpha-tocopherol and daidzein against d-galactosamine-induced oxidative damage in the rat liver.
We hypothesized that the hepatotoxicity that develops after the induction of oxidative stress (induced by d-galactosamine [GalN]) can be ameliorated by alpha-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.
Wong
Max C Y
MC
Nutritional Sciences Research Division, King's College London, SE1 9NH London, UK.
Portmann
Bernard
B
Sherwood
Roy
R
Niemela
Onni
O
Koivisto
Heidi
H
Parkkila
Seppo
S
Trick
Keith
K
L'abbe
Mary R
MR
Wilson
James
J
Dash
Philip R
PR
Srirajaskanthan
Raj
R
Preedy
Victor R
VR
Wiseman
Helen
H
D000818:Animals; D019610:Cytoprotection; D005688:Galactosamine / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology*
D007529:Isoflavones; D008315:Malondialdehyde; C004742:daidzein; D005688:Galactosamine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D024502:alpha-Tocopherol