Heme oxygenase induction by cadmium chloride: evidence for oxidative stress involvement.
Cadmium chloride (CdCl2), a well-known inducer of heme oxygenase, produced a strong increase in 'in vivo' rat liver chemiluminescence (QLV) 3 h after administration. Heme oxygenase activity increased 5 h after treatment, reaching a maximum value around 12-15 h after CdCl2 administration. Such induction was preceded by a decrease in the intrahepatic GSH pool and an increase in hydrogen peroxide steady-state concentration, both effects taking place several hours before induction of heme oxygenase. The activity of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) was found to be significantly decreased 5 h after CdCl2 injection. Administration of bilirubin, the end product of heme catabolism in mammals, and alpha-tocopherol, a widely employed antioxidant, prevented heme oxygenase induction as well as the decrease in hepatic GSH and the increase in chemiluminescence when administered 2 h before CdCl2 treatment. These results obtained with CdCl2 treatment support our recent reports correlating heme oxygenase induction with oxidative stress.
Ossola
J O
JO
Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Tomaro
M L
ML
D000818:Animals; D001663:Bilirubin / Q000097:blood; D002104:Cadmium / Q000633:toxicity*; D019256:Cadmium Chloride; D002273:Carcinogens / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D002712:Chlorides / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008163:Luminescent Measurements; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D002273:Carcinogens; D002712:Chlorides; D002104:Cadmium; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D006419:Heme Oxygenase (Decyclizing); D013482:Superoxide Dismutase; D005978:Glutathione; D019256:Cadmium Chloride; D001663:Bilirubin