Cigremis Yilmaz, Parlakpinar Hakan, Polat Alaadin, Colak Cemil, Ozturk Feral, Sahna Engin, Ermis Necip, Acet Ahmet
Department of Biology, Faculty of Art and Science, Kafkas University, Kars, Turkey.
Mol Cell Biochem. 2006 Apr;285(1-2):149-54. doi: 10.1007/s11010-005-9072-8. Epub 2006 Apr 13.
Doxorubicin (DOX) is a broad-spectrum anthracycline antibiotic that has cardiotoxicity as a major side effect. One mechanism of this toxicity is believed to involve the reactive oxygen radical species (ROS); these agents likely account for the pathophysiology of DOX-induced cardiomyopathy. Aminoguanidine (AG) is an effective antioxidant and free radical scavenger which has long been known to protect against ROS formation. We investigated the effects of AG on DOX-induced changes in thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content. The rats were divided into four groups:1) Control; 2) DOX group; injected intraperitoneally (i.p.) with DOX 20 mg/kg in a single dose 3) AG-treated group; injected i.p. in single dose of 20 mg/kg DOX plus 100 mg/kg AG 1 h before the DOX for 3 days, 4) AG group; injected i.p. with AG 100 mg/kg for 3 days. DOX administration to control rats increased TBARS and decreased GSH levels. AG administration before DOX injection caused significant decrease in TBARS and increase in GSH levels in the heart tissue when compared with DOX only. Morphological changes, including severe myocardial fibrosis and inflammatory cell infiltration were clearly observed in the DOX-treated heart. AG reversed the DOX-induced heart damage. Therefore AG could protect the heart tissue against free radical injury. The application of AG during cancer chemotherapy may attenuate tissue damage and improve the therapeutic index of DOX.
阿霉素（DOX）是一种广谱蒽环类抗生素，其主要副作用是具有心脏毒性。这种毒性的一种机制被认为涉及活性氧自由基（ROS）；这些物质可能是DOX诱导的心肌病病理生理学的原因。氨基胍（AG）是一种有效的抗氧化剂和自由基清除剂，长期以来已知其可防止ROS形成。我们研究了AG对DOX诱导的硫代巴比妥酸反应性物质（TBARS）和还原型谷胱甘肽（GSH）含量变化的影响。将大鼠分为四组：1）对照组；2）DOX组；腹腔注射（i.p.）单剂量20mg/kg的DOX 3）AG治疗组；在注射DOX前1小时腹腔注射单剂量20mg/kg的DOX加100mg/kg的AG，共3天，4）AG组；腹腔注射100mg/kg的AG，共3天。给对照大鼠注射DOX会增加TBARS并降低GSH水平。与仅注射DOX相比，在注射DOX前给予AG可使心脏组织中的TBARS显著降低，GSH水平升高。在DOX处理的心脏中清楚地观察到形态学变化，包括严重的心肌纤维化和炎性细胞浸润。AG逆转了DOX诱导的心脏损伤。因此，AG可以保护心脏组织免受自由基损伤。在癌症化疗期间应用AG可能会减轻组织损伤并提高DOX的治疗指数。
