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托吡酯和螺旋藻对阿霉素诱导的大鼠心脏毒性的保护作用。

The protective effects of topiramate and spirulina against doxorubicin-induced cardiotoxicity in rats.

作者信息

Elmorsi Radwa M, Kabel Ahmed M, El Saadany Amira A, Abou El-Seoud Samia H

机构信息

Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt.

出版信息

Hum Exp Toxicol. 2023 Jan-Dec;42:9603271231198624. doi: 10.1177/09603271231198624.

Abstract

Doxorubicin (DOX) is a widely used chemotherapy drug that can cause significant cardiotoxicity, limiting its clinical application. This study aimed to investigate the potential protective effects of topiramate (TPM) and spirulina (SP), either alone or in combination, in preventing DOX-induced cardiotoxicity. Adult Sprague Dawley rats were divided into five groups, including a normal control group and groups receiving DOX alone, DOX with TPM, DOX with SP, or DOX with a combination of TPM and SP. Cardiotoxicity was induced by administering DOX intraperitoneally at a cumulative dose of 16 mg/kg over 4 weeks. TPM and/or SP administration started 1 week before DOX treatment and continued for 35 days. Body weight, serum markers of cardiac damage, oxidative stress and inflammatory parameters were assessed. Histopathological and immunohistochemical examinations were performed on cardiac tissues. Results showed that TPM and SP monotherapy led to significant improvements in serum levels of cardiac markers, decreased oxidative stress, reduced fibrosis-related growth factor levels, increased antioxidant levels, and improved histopathological features. SP demonstrated more prominent effects in comparison to TPM, and the combination of TPM and SP exhibited even more pronounced effects. In conclusion, TPM and SP, either alone or in combination, hold promise as therapeutic interventions for mitigating DOX-induced cardiotoxicity.

摘要

阿霉素(DOX)是一种广泛使用的化疗药物,可导致显著的心脏毒性,限制了其临床应用。本研究旨在探讨托吡酯(TPM)和螺旋藻(SP)单独或联合使用对预防DOX诱导的心脏毒性的潜在保护作用。成年Sprague Dawley大鼠分为五组,包括正常对照组以及单独接受DOX、DOX与TPM联用、DOX与SP联用或DOX与TPM和SP联用的组。通过在4周内腹腔注射累积剂量为16 mg/kg的DOX来诱导心脏毒性。在DOX治疗前1周开始给予TPM和/或SP,并持续35天。评估体重、心脏损伤的血清标志物、氧化应激和炎症参数。对心脏组织进行组织病理学和免疫组织化学检查。结果表明,TPM和SP单药治疗可显著改善心脏标志物的血清水平,降低氧化应激,降低纤维化相关生长因子水平,提高抗氧化剂水平,并改善组织病理学特征。与TPM相比,SP表现出更显著的效果,TPM和SP联合使用表现出更明显的效果。总之,TPM和SP单独或联合使用有望作为减轻DOX诱导的心脏毒性的治疗干预措施。

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