Efficacy of sulfhydryl compounds as inhibitors of iron-dependent doxorubicin-enhanced lipid peroxidation.
The ability of sulfhydryl compounds to inhibit doxorubicin enhanced lipid peroxidation in the presence of added iron was evaluated. Optimal conditions for doxorubicin-enhanced lipid peroxidation were 25 microM doxorubicin, 2 mM ADP and 250 microM ferric chloride at pH 8.0. Lipid peroxidation was inhibited by EDTA (500 microM), SKF 525 A (100 microM) and vitamin E (0.1 unit/ml). Cysteamine (1 mM) stimulated basal lipid peroxidation but produced net inhibition of lipid peroxidation with doxorubicin. Cysteamine (10 mM) was more efficacious at inhibiting lipid peroxidation. N-acetylcysteine at 1 and 10 mM was a potent stimulator of lipid peroxidation and was ineffective at inhibiting lipid peroxidation in the presence of doxorubicin either at optimal or suboptimal concentrations of iron. In contrast, glutathione (1 mM) was a potent inhibitor of lipid peroxidation. The data suggests that N-acetylcysteine protects against doxorubicin by prior conversion to glutathione.
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D003543:Cysteamine / Q000494:pharmacology; D004317:Doxorubicin / Q000633:toxicity*; D005978:Glutathione / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D011817:Rabbits; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D008054:Lipid Peroxides; D013438:Sulfhydryl Compounds; D003543:Cysteamine; D004317:Doxorubicin; D007501:Iron; D005978:Glutathione; D000111:Acetylcysteine