Protective effects of the angiotensin II receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress, and early ventricular impairment
Protective effects of the angiotensin II receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress, and early ventricular impairment
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DOI：
10.1016/j.ahj.2010.05.037
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发表时间：
2010-09-01
影响因子：
4.8
通讯作者：
Mercuro, Giuseppe
中科院分区：
文献类型：
--
作者：
Cadeddu, Christian;Piras, Alessandra;Mercuro, Giuseppe
研究背景氧化应激和RAAS在蒽环类药物心脏毒性的发生中起重要作用。替米沙坦是一种血管紧张素Ⅱ 1型受体阻滞剂，可抑制超氧阴离子源的激活，并诱导抗炎作用。方法观察替米沙坦对表阿霉素（EPI）所致心肌损伤的保护作用。49例无心血管疾病的各种实体癌的影响进行了检查。合格患者从化疗前1周开始随机接受替米沙坦（40 mg/d; TEL，n = 25）或安慰剂（PLA，n = 24）。通过超声心动图、组织多普勒、应变和应变率（SR）成像对患者进行研究。我们还测量了炎症和氧化应激标志物的血浆水平。结果EPI剂量为200 mg/m2时，SR峰值受损，TEL和PLA之间无显著差异（1.41 +/- 0.31 vs 1.59 +/- 0.36/s）。随着EPI累积剂量的增加，SR仅在TEL中正常化，与EPI剂量为300 mg/m2的PLA相比显示出显著差异（2）（1.69 +/- 0.42 vs 1.34 +/- 0.18/s，P < .001）和400 mg/m2（1.74 +/- 0.27 vs 1.38 +/- 0.24/s，P < .001）。此外，活性氧和白细胞介素-6显着增加，发现在PLA，但这些保持不变，在TEL.Conclusions我们证实，EPI诱导的心脏毒性主要与心脏抗氧化防御的失活。此外，我们发现替米沙坦可以减少EPI诱导的自由基，拮抗炎症反应，逆转早期心肌损伤。(Am Heart J 2010; 160：487.
Background Oxidative stress and RAAS play an important role in the occurrence of anthracyclines-induced cardiotoxicity. Telmisartan, an angiotensin II type 1 receptor blocker, inhibits activation of superoxide sources and induces anti-inflammatory effects.Methods The possible role of telmisartan in preventing myocardial damage induced by epirubicin (EPI) was investigated. Forty-nine patients free from cardiovascular diseases affected by a variety of solid cancers were examined. Eligible patients were randomized to receive telmisartan (40 mg/d; TEL, n = 25) or placebo (PLA, n = 24) starting 1 week before chemotherapy. Patients were studied by means of echocardiography, tissue Doppler, and strain and strain rate (SR) imaging. We also measured plasma levels of inflammatory and oxidative stress markers. All parameters were assessed at baseline and 7 days after every new EPI dose of 100 mg/m(2).Results An impairment of the SR peak was observed at the EPI dose of 200 mg/m(2), with no significant differences between TEL and PLA (1.41 +/- 0.31 vs 1.59 +/- 0.36/s). At growing cumulative doses of EPI, SR normalized only in TEL, showing a significant difference in comparison to PLA at EPI doses of 300 mg/m(2) (1.69 +/- 0.42 vs 1.34 +/- 0.18/s, P < .001) and 400 mg/m(2) (1.74 +/- 0.27 vs 1.38 +/- 0.24/s, P < .001). Moreover, a significant increase in reactive oxygen species and interleukin-6 was found in PLA; but these remained unchanged in TEL.Conclusions We confirmed that EPI-induced cardiotoxicity is primarily related to the inactivation of the cardiac antioxidant defenses. In addition, we showed that telmisartan can reduce EPI-induced radical species, antagonize the inflammation, and reverse the early myocardial impairment. (Am Heart J 2010; 160:487.e1-487.e7.)