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.