Protective effect of Sn-protoporphyrin against doxorubicin-induced perturbations of heme metabolism.
The administration of doxorubicin, an anti-tumor antibiotic, to rodents resulted in an increase in heme oxygenase activity and a decrease in delta-aminolevulinate (ALA) synthase activity and in cellular heme and cytochrome P450 content in liver. Sn-protoporphyrin, a potent inhibitor of heme degradation both in vitro and in vivo, when administered to rodents prior to doxorubicin, mitigates the drug-induced toxic actions which are reflected by the drug-induced decreases of both cellular heme and cytochrome P450 content. Sn-protoporphyrin thus provides a pharmacological means of protecting against the toxic effects of doxorubicin and other drugs which enhance heme oxygenase activity and thus decrease cellular heme and cytochrome P450 content in vivo.
Wissel
P S
PS
Rockefeller University Hospital, New York, New York 10021.
Drummond
G S
GS
Kappas
A
A
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology* / Q000633:toxicity; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology* / Q000627:therapeutic use; D011524:Protoporphyrins / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains
D008665:Metalloporphyrins; D011524:Protoporphyrins; D006418:Heme; D004317:Doxorubicin; D003577:Cytochrome P-450 Enzyme System; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D000624:5-Aminolevulinate Synthetase