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.