Demonstration that the temporary sequestering of adventitious iron accounts for the inhibition of microsomal lipid peroxidation by bleomycin A2.
One of the manifestations of the interaction of bleomycin with the microsomal mixed-function oxidase system is an inhibition of NADPH-dependent, reactive oxygen-mediated lipid peroxidation. The results of this investigation demonstrate that this effect by bleomycin can be attributed to the sequestering of adventitious iron. However, as a result of the microsome-catalyzed, iron-facilitated activation of bleomycin and the concomitant spontaneous decay of the activated bleomycin intermediate, iron can apparently no longer be bound by the bleomycin molecule; consequently, the inhibition of microsomal lipid peroxidation by bleomycin is only temporary.
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism; D003855:Deoxyribose / Q000378:metabolism; D004492:Edetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D008054:Lipid Peroxides; D001761:Bleomycin; D008315:Malondialdehyde; D003855:Deoxyribose; D003300:Copper; D004492:Edetic Acid; D007501:Iron