Heme oxygenase induction by menadione bisulfite adduct-generated oxidative stress 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 administration. To evaluate liver antioxidant enzymatic defenses, superoxide dismutase, catalase and glutathione peroxidase activities were determined. Antioxidant enzymes significantly decreased 3 h after menadione bisulfite adduct injection. Heme oxygenase activity appeared 6 h after treatment, peaking 9 h after menadione bisulfite adduct 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 some hours before induction of heme oxygenase. Iron ferritin levels and ferritin content began to increase 6 h after heme oxygenase induction, and these increases were significantly higher 15 h after treatment and remained high for at least 24 h after menadione bisulfite adduct injection. Administration of bilirubin entirely prevented heme oxygenase induction as well as the decrease in hepatic GSH and the increase in lipid peroxidation when administered 2 h before menadione bisulfite adduct treatment. These results indicate that the induction of heme oxygenase by menadione bisulfite adduct may be a general response to oxidant stress, by increasing bilirubin and ferritin levels and could therefore provide a major cellular defense mechanism against oxidative damage.
Ossola
J O
JO
Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Kristoff
G
G
Tomaro
M L
ML
D000818:Animals; D002374:Catalase / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D005293:Ferritins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D006490:Hemostatics / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014812:Vitamin K / Q000031:analogs & derivatives* / Q000494:pharmacology; D024483:Vitamin K 3
D006490:Hemostatics; D014812:Vitamin K; D024483:Vitamin K 3; D005293:Ferritins; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D006419:Heme Oxygenase (Decyclizing); D013482:Superoxide Dismutase; D005978:Glutathione