Plasma nitric oxide levels used as an indicator of doxorubicin-induced cardiotoxicity in rats
Plasma nitric oxide levels used as an indicator of doxorubicin-induced cardiotoxicity in rats
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DOI：
10.1038/sj.thj.6200573
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Crespo, MJ
中科院分区：
文献类型：
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作者：
Guerra, J;De Jesus, A;Crespo, MJ
简介：阿霉素的临床疗效因其心脏毒性而受到严重限制。目前用于检测这种并发症的非侵入性技术缺乏识别其早期阶段的敏感性。一氧化氮 (NO) 是一种自由基，与阿霉素引起的心脏毒性的病因有关。在本研究中，我们研究血浆NO水平是否可以用作阿霉素诱导的心脏毒性的无创且可靠的生物标志物。材料和方法：实验使用两组6只自发性高血压大鼠(SHR)。第 1 组每周接受 1.5 mg/kg 腹膜内 (IP) 多柔比星治疗，持续长达 9 周。第 2 组（对照组）每周接受 9 次腹腔注射 0.5 cm(3) 盐水。测定血浆NO水平和心脏射血分数(EF%)。根据 Billinghan 评分，通过光学显微镜对心室活检进行分析。 结果：阿霉素治疗显着增加血浆 NO 浓度（对照动物中为 35.30+/-5.63 muM 对比 14.72+/-2.66 muM，n = 6，P < 0.05）。此外，阿霉素使 EF 降低约 23%（从对照组的 77.00+/-3.89 到阿霉素治疗动物的 59.00+/-5.61，n = 6，P < 0.05）。多柔比星治疗组的组织学心脏损伤平均评分为 2.33+/-0.33，对照组为 0.08+/-0.08，n = 6，P < 0.001。讨论：我们的结果揭示了血浆 NO 水平、收缩功能和组织病理学心肌损伤之间的相关性。因此，血浆 NO 水平可以用作阿霉素治疗的 SHR 心肌损伤的生物标志物，并且可能是无创评估阿霉素诱导的人类毒性的潜在工具。
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 (35.30+/-5.63 muM versus 14.72+/-2.66 muM in control animals, n = 6, P < 0.05). In addition, doxorubicin decreased EF by 23% approximately (from 77.00+/-3.89 in controls, to 59.00+/-5.61 in doxorubicin-treated animals, n = 6, P < 0.05). The mean score of histological cardiac damage was 2.33+/-0.33 for doxorubicin-treated versus 0.08+/-0.08 for controls, n = 6, P < 0.001.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.