Abstract:
:Bleomycin has a long-studied mechanism of action through the formation of a complex with metals, such as iron. The bleomycin-iron complex was recently shown to induce membrane damage by free radical reactivity. Because the use of Fe nanoparticles is spreading for drug delivery strategies, molecular mechanisms of cell damage must include different compartments in order to observe the progression of the cell reactivity. In this study, human embryonic kidney (HEK-293) cells were exposed for 24 h to bleomycin and polymeric iron oxide nanoparticles (Fe-NPs), alone or in combination. The fatty acid-based membrane lipidomic analysis evidenced the fatty acid remodeling in response to the treatments. Bleomycin alone caused the increase of saturated fatty acid (SFA) moieties in cell membrane glycerophospholipids with concomitant diminution of monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acid levels. Under Fe-NPs treatment, omega-6 PUFA decreased and trans fatty acid isomers increased. Under coadministration bleomycin and Fe-NPs, all membrane remodeling changes disappeared compared to those of the controls, with only an increase of omega-6 PUFA that elevates peroxidation index remaining. Our results highlight the important role of fatty-acid-based membrane lipidome monitoring to follow up the fatty acid reorganization induced by the drug, to be considered as a side effect of the pharmacological activity, suggesting the need of an integrated approach for the investigation of drug and carrier molecular mechanisms.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Krokidis MG,Louka M,Efthimiadou EK,Ferreri C,Chatgilialoglu Cdoi
10.1021/acs.chemrestox.0c00162subject
Has Abstractpub_date
2020-10-19 00:00:00pages
2565-2572issue
10eissn
0893-228Xissn
1520-5010journal_volume
33pub_type
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