罗舒伐他汀对阿奇霉素诱导的大鼠模型心脏毒性的保护作用。
Protective effect of Rosuvastatin on Azithromycin induced cardiotoxicity in a rat model.
机构信息
Anatomy Department, Faculty of Medicine, Suez Canal University, Egypt.
Anatomy Department, Faculty of Medicine, Suez Canal University, Egypt.
出版信息
Life Sci. 2021 Mar 15;269:119099. doi: 10.1016/j.lfs.2021.119099. Epub 2021 Jan 19.
AIMS
Azithromycin is widely used broad spectrum antibiotic recently used in treatment protocol of COVID-19 for its antiviral and immunomodulatory effects combined with Hydroxychloroquine or alone. Rat models showed that Azithromycin produces oxidative stress, inflammation, and apoptosis of myocardial tissue. Rosuvastatin, a synthetic statin, can attenuate myocardial ischemia with antioxidant and antiapoptotic effects. This study aims to evaluate the probable protective effect of Rosuvastatin against Azithromycin induced cardiotoxicity.
MAIN METHOD
Twenty adult male albino rats were divided randomly into four groups, five rats each control, Azithromycin, Rosuvastatin, and Azithromycin +Rosuvastatin groups. Azithromycin 30 mg/kg/day and Rosuvastatin 2 mg/kg/day were administrated for two weeks by an intragastric tube. Twenty-four hours after the last dose, rats were anesthetized and the following measures were carried out; Electrocardiogram, Blood samples for Biochemical analysis of lactate dehydrogenase (LDH), and creatine phosphokinase (CPK). The animals sacrificed, hearts excised, apical part processed for H&E, immunohistochemical staining, and examined by light microscope. The remaining parts of the heart were collected for assessment of Malondialdehyde (MDA) and Reduced Glutathione (GSH).
KEY FINDINGS
The results revealed that Rosuvastatin significantly ameliorates ECG changes, biochemical, and Oxidative stress markers alterations of Azithromycin. Histological evaluation from Azithromycin group showed marked areas of degeneration, myofibers disorganization, inflammatory infiltrate, and hemorrhage. Immunohistochemical evaluation showed significant increase in both Caspase 3 and Tumor necrosis factor (TNF) immune stain. Rosuvastatin treated group showed restoration of the cardiac muscle fibers in H&E and Immunohistochemical results.
SIGNIFICANCE
We concluded that Rosuvastatin significantly ameliorates the toxic changes of Azithromycin on the heart.
目的
阿奇霉素是一种广泛应用的广谱抗生素，最近因其抗病毒和免疫调节作用而被用于 COVID-19 的治疗方案中，与羟氯喹联合或单独使用。大鼠模型表明，阿奇霉素会导致心肌组织产生氧化应激、炎症和细胞凋亡。瑞舒伐他汀是一种合成他汀类药物，具有抗氧化和抗凋亡作用，可以减轻心肌缺血。本研究旨在评估瑞舒伐他汀对阿奇霉素诱导的心肌毒性的可能保护作用。
主要方法
将 20 只成年雄性白化大鼠随机分为四组，每组 5 只，分别为对照组、阿奇霉素组、瑞舒伐他汀组和阿奇霉素+瑞舒伐他汀组。通过灌胃给药，阿奇霉素组给予 30mg/kg/天，瑞舒伐他汀组给予 2mg/kg/天，连续给药两周。最后一次给药 24 小时后，麻醉大鼠，进行以下检测：心电图、血样用于乳酸脱氢酶（LDH）和肌酸磷酸激酶（CPK）的生化分析。处死动物，取出心脏，心尖部分用于 H&E、免疫组织化学染色，并在光镜下检查。心脏的其余部分用于评估丙二醛（MDA）和还原型谷胱甘肽（GSH）。
主要发现
结果表明，瑞舒伐他汀能显著改善阿奇霉素引起的心电图变化、生化和氧化应激标志物改变。阿奇霉素组的组织学评价显示，有明显的退行性变区域、肌纤维结构紊乱、炎症浸润和出血。免疫组织化学评价显示，Caspase 3 和肿瘤坏死因子（TNF）免疫染色均显著增加。瑞舒伐他汀治疗组在 H&E 和免疫组织化学结果中显示心肌纤维得到了恢复。
意义
我们得出结论，瑞舒伐他汀能显著改善阿奇霉素对心脏的毒性作用。
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