Heme oxygenase and oxidative stress. Evidence of involvement of bilirubin as physiological protector against oxidative damage.
Cobalt chloride (CoCl2), a well-known inducer of heme oxygenase, produced a strong increase of in vivo rat liver chemiluminescence (QLV) 6 h after its administration. The activity of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) was found to be significantly decreased 9 h after CoCl2 injection. Heme oxygenase activity increased 9 h after treatment, reaching a maximum value around 18 to 24 h after CoCl2 administration. This 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 the heme-oxygenase. Co-administration of Sn-protoporphyrin IX, a potent inhibitor of heme oxygenase, completely prevented the enzyme induction, increasing the QLV levels. Administration of bilirubin, the end product of heme catabolism in mammals, prevented the heme oxygenase induction as well as the decrease in hepatic GSH and the increase of chemiluminescence when it was administered 2 h before CoCl2 treatment. These results support the proposal that the induction of heme oxygenase by cobalt chloride may be a general response to oxidant stress and, by increasing bilirubin levels, could constitute an important cellular defense mechanism against oxidative damage.
Llesuy
S F
SF
Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Tomaro
M L
ML
D000818:Animals; D001663:Bilirubin / Q000502:physiology*; D003035:Cobalt / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000032:analysis; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D006861:Hydrogen Peroxide / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000201:enzymology*; D008163:Luminescent Measurements; D016877:Oxidants / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D016877:Oxidants; D003035:Cobalt; D006861:Hydrogen Peroxide; D006419:Heme Oxygenase (Decyclizing); C018021:cobaltous chloride; D005978:Glutathione; D001663:Bilirubin