Heme oxygenase induction by menadione bisulfite adduct-generated oxidativestress in rat liver

The in vivo effect of menadione bisulfite adduct on both hepatic oxidative stress and heme oxygenase induction was studied. A marked increase in lipid peroxidation was observed 1 h after menadione bisulfite adduct administrat ion. To evaluate liver antioxidant enzymatic defenses, superoxide dismutase , catalase and glutathione peroxidase activities were determined. Antioxida nt enzymes significantly decreased 3 h after menadione bisulfite adduct inj ection. Heme oxygenase activity appeared 6 h after treatment, peaking 9 h a fter menadione bisulfite adduct administration. Such induction was preceded by a decrease in the intrahepatic GSH pool and an increase in hydrogen per oxide steady-state concentration, both effects taking place some hours befo re induction of heme oxygenase. Iron ferritin levels and ferritin content b egan to increase 6 h after heme oxygenase induction, and these increases we re significantly higher 15 h after treatment and remained high for at least 24 h after menadione bisulfite adduct injection. Administration of bilirub in entirely prevented heme oxygenase induction as well as the decrease in h epatic GSH and the increase in lipid peroxidation when administered 2 h bef ore menadione bisulfite adduct treatment. These results indicate that the i nduction of heme oxygenase by menadione bisulfite adduct may be a general r esponse to oxidant stress? by increasing bilirubin and ferritin levels and could therefore provide a major cellular defense mechanism against oxidativ e damage. (C) 2000 Elsevier Science Inc. All rights reserved.