Relationship between oxidative stress and heme oxygenase induction by copper sulfate.
The effect of copper sulfate (CuSO4) on both hepatic oxidative stress and heme oxygenase induction was studied. A strong increase in in vivo rat liver chemiluminescence was observed 1 h after Cu(II) administration. To evaluate liver antioxidant enzymatic defenses, superoxide dismutase, catalase, and glutathione peroxidase activities were determined. Catalase and glutathione peroxidase were found to be significantly decreased 5 h after CuSO4 injection. In contrast, superoxide dismutase activity was increased. Heme oxygenase activity appeared 5 h after treatment, reaching a maximum value 18 h after CuSO4 administration. This induction was preceded by a decrease in the intrahepatic GSH pool and an increase in the generation of thiobarbituric acid reactive substances, both effects taking place a number of hours before induction of heme oxygenase. Administration of bilirubin, the end product of heme catabolism in mammals, and alpha-tocopherol, a widely employed antioxidant, completely prevented heme oxygenase induction as well as the decrease in hepatic GSH and the increase in chemiluminescence when administered 2 h before CuSO4 treatment. Under the same experimental conditions, beta-carotene showed a moderate preventive effect on both heme oxygenase induction and oxidative stress parameters. These data obtained with Cu(II) treatment are in agreement with our previous reports suggesting a correlation between heme oxygenase induction and oxidative stress.
Ossola
J O
JO
Departamento de Química Biológica, Facultad de Farmacia y Bioquímica,Universidad de Buenos Aires, Argentina.
Groppa
M D
MD
Tomaro
M L
ML
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001663:Bilirubin / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D019327:Copper Sulfate / Q000494:pharmacology*; D004790:Enzyme Induction; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D002374:Catalase; D005979:Glutathione Peroxidase; D006419:Heme Oxygenase (Decyclizing); D013482:Superoxide Dismutase; D005978:Glutathione; D019327:Copper Sulfate; D001663:Bilirubin