Yagmurca Murat, Fadillioglu Ersin, Erdogan Hasan, Ucar Muharrem, Sogut Sadik, Irmak M Kemal
Department of Histology and Embryology, Medical Faculty of Afyon Kocatepe University, Afyon, Turkey.
Pharmacol Res. 2003 Oct;48(4):377-82. doi: 10.1016/s1043-6618(03)00185-3.
The clinical use of doxorubicin (Dxr) is limited by its cardiotoxic effects which are mediated by oxygen radicals. The purpose of this study was to investigate in vivo protective effects of erdosteine, an antioxidant agent because of its secondary active metabolites in vivo, against the cardiotoxicity induced by Dxr in rats. Three groups of male Sprague-Dawley rats (60 days old) were used. Group 1 was untreated group used as control; the other groups were treated with Dxr (single i.p. dosage of 20 mg kg(-1) b.wt.) or Dxr plus erdosteine (10 mg kg(-1) day(-1), orally), respectively. Erdosteine or oral saline treatment was done starting 2 days before Dxr for 12 days. The analyses were done at the 10th day of Dxr treatment. The protein carbonyl content, the activities of myeloperoxidase, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK) as well as heart rate and blood pressures were significantly increased in Dxr group in comparison with the other groups. However, pulse pressure was decreased in Dxr group. The body and heart weights were decreased in both Dxr administered groups in comparison with control group. Disorganization of myocardial histology, picnotic nuclei, edema, and increase in collagen content around vessels were seen in the slides of Dxr group, whereas normal myocardial microscopy was preserved in Dxr plus erdosteine group. Collectively, these in vivo hemodynamic, enzymatic and morphologic studies provide an evidence for a possible prevention of cardiac toxicity in Dxr-treated patients.
阿霉素（Dxr）的临床应用因其由氧自由基介导的心脏毒性作用而受到限制。本研究的目的是研究厄多司坦（一种因其体内二级活性代谢产物而具有抗氧化作用的药物）对大鼠阿霉素诱导的心脏毒性的体内保护作用。选用三组雄性Sprague-Dawley大鼠（60日龄）。第1组为未处理组作为对照；其他两组分别用阿霉素（腹腔注射单次剂量20 mg·kg⁻¹体重）或阿霉素加厄多司坦（10 mg·kg⁻¹·天⁻¹，口服）处理。在阿霉素给药前2天开始给予厄多司坦或口服生理盐水，持续12天。在阿霉素治疗的第10天进行分析。与其他组相比，阿霉素组的蛋白质羰基含量、髓过氧化物酶、天冬氨酸转氨酶（AST）、乳酸脱氢酶（LDH）和肌酸激酶（CK）的活性以及心率和血压均显著升高。然而，阿霉素组的脉压降低。与对照组相比，两个给予阿霉素的组的体重和心脏重量均降低。在阿霉素组的切片中可见心肌组织学紊乱、核固缩、水肿以及血管周围胶原含量增加，而在阿霉素加厄多司坦组中保留了正常的心肌显微镜检查结果。总体而言，这些体内血流动力学、酶学和形态学研究为预防阿霉素治疗患者的心脏毒性提供了可能的证据。
