BACKGROUND AND PURPOSE: The anticancer drugs doxorubicin and bleomycin are well-known for their oxidative stress-mediated side effects in heart and lung, respectively. It is frequently suggested that iron is involved in doxorubicin and bleomycin toxicity. We set out to elucidate whether iron chelation prevents the oxidative stress-mediated toxicity of doxorubicin and bleomycin and whether it affects their antiproliferative/proapoptotic effects. EXPERIMENTAL APPROACH: Cell culture experiments were performed in A549 cells. Formation of hydroxyl radicals was measured in vitro by electron paramagnetic resonance (EPR). We investigated interactions between five iron chelators and the oxidative stress-inducing agents (doxorubicin, bleomycin and H(2)O(2)) by quantifying oxidative stress and cellular damage as TBARS formation, glutathione (GSH) consumption and lactic dehydrogenase (LDH) leakage. The antitumour/proapoptotic effects of doxorubicin and bleomycin were assessed by cell proliferation and caspase-3 activity assay. KEY RESULTS: All the tested chelators, except for monohydroxyethylrutoside (monoHER), prevented hydroxyl radical formation induced by H(2)O(2)/Fe(2+) in EPR studies. However, only salicylaldehyde isonicotinoyl hydrazone and deferoxamine protected intact A549 cells against H(2)O(2)/Fe(2+). Conversely, the chelators that decreased doxorubicin and bleomycin-induced oxidative stress and cellular damage (dexrazoxane, monoHER) were not able to protect against H(2)O(2)/Fe(2+). CONCLUSIONS AND IMPLICATIONS: We have shown that the ability to chelate iron as such is not the sole determinant of a compound protecting against doxorubicin or bleomycin-induced cytotoxicity. Our data challenge the putative role of iron and hydroxyl radicals in the oxidative stress-mediated cytotoxicity of doxorubicin and bleomycin and have implications for the development of new compounds to protects against this toxicity.

• MeSH
• aldehydy farmakologie   MeSH
• apoptóza účinky léků   MeSH
• bleomycin toxicita   MeSH
• časové faktory MeSH
• chelátory železa chemie   farmakologie   MeSH
• deferoxamin farmakologie   MeSH
• doxorubicin toxicita   MeSH
• elektronová paramagnetická rezonance MeSH
• hydrazony farmakologie   MeSH
• isoniazid analogy a deriváty   farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory plic metabolismus   patologie   MeSH
• oxidační stres účinky léků   MeSH
• peroxid vodíku chemie   MeSH
• peroxidace lipidů účinky léků   MeSH
• proliferace buněk účinky léků   MeSH
• protinádorová antibiotika toxicita   MeSH
• pyridoxal analogy a deriváty   farmakologie   MeSH
• razoxan farmakologie   MeSH
• sloučeniny železa chemie   metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• volné radikály chemie   MeSH
• železo chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aldehydy MeSH
• bleomycin MeSH
• chelátory železa MeSH
• deferoxamin MeSH
• doxorubicin MeSH
• Fenton's reagent MeSH Prohlížeč
• hydrazony MeSH
• isoniazid MeSH
• peroxid vodíku MeSH
• protinádorová antibiotika MeSH
• pyridoxal isonicotinoyl hydrazone MeSH Prohlížeč
• pyridoxal MeSH
• razoxan MeSH
• salicylaldehyde isonicotinoyl hydrazone MeSH Prohlížeč
• sloučeniny železa MeSH
• volné radikály MeSH
• železo MeSH