Plasma nitric oxide levels used as an indicator of doxorubicin-induced cardiotoxicity in rats
| Autor: | Angel Roman-Franco, Jhon A. Guerra, Ana De Jesus, Edwin Rodríguez, Maria J Crespo, Pedro J. Santiago-Borrero |
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| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty Systole medicine.medical_treatment Urology Nitric Oxide Nitric oxide chemistry.chemical_compound Rats Inbred SHR Medicine Animals Doxorubicin Saline Cardiotoxicity Ejection fraction business.industry Myocardium Heart Hematology Rats chemistry Echocardiography Anesthesia Toxicity Models Animal Biomarker (medicine) business Biomarkers medicine.drug |
| Zdroj: | The hematology journal : the official journal of the European Haematology Association. 5(7) |
| ISSN: | 1466-4860 |
| Popis: | Introduction: The clinical efficacy of doxorubicin is severely limited by its cardiotoxicity. The currently noninvasive techniques used to detect this complication lack sensitivity to identify its early stages. Nitric oxide (NO) is a free radical that has been implicated in the etiology of doxorubicin-induced cardiotoxicity. In the present study, we investigated whether plasmatic NO levels can be used as a noninvasive and reliable biomarker of doxorubicin-induced cardiotoxicity. Materials and methods: Two groups of six spontaneously hypertensive rats (SHR) were used for the experiment. Group 1 received 1.5 mg/kg intraperitoneal (IP) doxorubicin weekly for up to 9 weeks. Group 2 (Control) received nine weekly IP injection of 0.5 cm 3 saline. Plasmatic NO levels and cardiac ejection fraction (EF%) were determined. Ventricular biopsies were analyzed by light microscopy according with the Billinghan score. Results: Doxorubicin treatment significantly increased plasmatic NO concentration (35.3075.63mM versus 14.7272.66mM in control animals, n ¼ 6, Po0.05). In addition, doxorubicin decreased EF by 23% approximately (from 77.0073.89 in controls, to 59.0075.61 in doxorubicin-treated animals, n ¼ 6, Po0.05). The mean score of histological cardiac damage was 2.3370.33 for doxorubicin-treated versus 0.0870.08 for controls, n ¼ 6, Po0.001. Discussion: Our results revealed a correlation between plasmatic NO levels, systolic function and histopathological myocardial damage. Therefore, it is plausible to postulate that plasmatic NO levels could be used as a biomarker for myocardial damage in doxorubicin-treated SHR, and may be a potential tool for noninvasive evaluation of doxorubicin-induced toxicity in humans. The Hematology Journal (2005) 5, 584–588. doi:10.1038/sj.thj.6200573 |
| Databáze: | OpenAIRE |
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