Hepatic enzymatic metabolism alterations and oxidative stress during the onset of carcinogenesis: protective role of alpha-tocopherol.
Oxidants play a role in several stages of carcinogenesis. A high antioxidant capacity is expected to protect 'initiated' cells from excessive oxidant toxicity. The aim of this study was to determine the chemopreventive effect of a-tocopherol (alpha-T) on the hepatocarcinogenesis induced with p-dimethylaminoazobenzene (DAB) in mice. The dietary administration of alpha-T completely reversed the induction of delta-aminolevulinate synthetase and glutathione-S-transferase (the tumoral marker enzyme). alpha-T greatly enhanced P 450 levels, which were even higher in animals exposed to DAB. Indirect evidence for the involvement of oxygen radicals in the DAB model of hepatocarcinogenesis was provided by increased levels of thiobarbituric acid reactive species, which were detected in animals with severe liver damage and were assessed by histological analysis. alpha-T reduced the degree of hepatic injury, although this vitamin produced only slight changes in the oxidative parameters evaluated. The use of alpha-T as a potential chemopreventive agent, particularly during the initiation stage of carcinogenesis provoked by DAB, is worthy of further study.
Gerez
E
E
Centro de Investigaciones sobre Porfirinas y Porfirias, (CONICET-FCEN, UBA), Ciudad Universitaria, Buenos Aires, Argentina.
Caballero
F
F
Vazquez
E
E
Polo
C
C
Batlle
A M
AM
D000624:5-Aminolevulinate Synthetase / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002273:Carcinogens; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D014810:Vitamin E / Q000494:pharmacology*; D004124:p-Dimethylaminoazobenzene
D000975:Antioxidants; D002273:Carcinogens; D014810:Vitamin E; D004124:p-Dimethylaminoazobenzene; D000624:5-Aminolevulinate Synthetase; D005982:Glutathione Transferase