Pyridoxal isonicotinoyl hydrazone (PIH) and its analogs as protectants against anthracycline-induced cardiotoxicity
Language English Country England, Great Britain Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
18274998
DOI
10.1080/03630260701680276
PII: 790612281
Knihovny.cz E-resources
- MeSH
- Iron Chelating Agents administration & dosage chemistry therapeutic use MeSH
- Daunorubicin administration & dosage toxicity MeSH
- Isoniazid administration & dosage analogs & derivatives chemistry therapeutic use MeSH
- Cardiotonic Agents administration & dosage chemistry therapeutic use MeSH
- Rabbits MeSH
- Heart Diseases chemically induced mortality prevention & control MeSH
- Antibiotics, Antineoplastic administration & dosage toxicity MeSH
- Pyridoxal administration & dosage analogs & derivatives chemistry therapeutic use MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Iron Chelating Agents MeSH
- Daunorubicin MeSH
- Isoniazid MeSH
- Cardiotonic Agents MeSH
- Antibiotics, Antineoplastic MeSH
- pyridoxal isonicotinoyl hydrazone MeSH Browser
- Pyridoxal MeSH
The risk of cardiotoxicity is the main drawback of anthracycline antibiotics. However, these drugs remain among the most effective and frequently used anti cancer drugs. In this study we aimed to assess the cardioprotective effects of aroylhydrazone iron (FE) chelators: pyridoxal isonicotinoyl hydrazone (PIH) and its two analogs: salicyladehyde isonicotinoyl hydrazone (SIH) and pyridoxal o-chlorbenzoyl hydrazone (o-108). In rabbits, chronic treatment with daunorubicin (DAU) (3 mg/kg weekly for 10 weeks) induced mortality (33%) as well as left ventricular (LV) dysfunction. Co-administrations of PIH (25 mg/kg, i.p.), SIH hydrochloride [1 mg/kg, iv] as well as o-108 (10 mg/kg, i.p.), fully prevented premature deaths and most of the DAU-induced functional impairments were significantly suppressed. However, when 2- to 2.5-fold higher doses of the chelators were used, they led to rather paradoxical and mostly negative results regarding both cardioprotection and overall mortality.
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