Protective effects of silymarin and curcumin on cyclophosphamide-induced cardiotoxicity

Q2 Medicine

Experimental and Toxicologic Pathology Pub Date : 2017-06-14 DOI:10.1016/j.etp.2017.02.002

H. Avci , E.T. Epikmen , E. Ipek , R. Tunca , S.S. Birincioglu , H. Akşit , S. Sekkin , A.N. Akkoç , M. Boyacioglu

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引用次数: 55

Abstract

Introduction

Cyclophosphamide (CP) is a potent anticancer agent; its clinical use is limited due to its marked cardiotoxicity.

Aim

The present study was aimed at evaluating the cardioprotective effects of silymarin (SLY) and curcumin (CUR), which have strong antioxidant properties, against the toxic effects of high-dose CP on the heart of rats.

Materials and methods

A total of 36 adult Wistar albino female rats were randomly divided into six groups. Group I (control group; nothing was administered), Group II (CP group; 30 mg/kg/day CP was administered intraperitoneally to each animal for seven days), Group III (SLY group; 100 mg/kg/day SLY by gavage for 14 days), Group IV (CUR group; 100 mg/kg/day CUR by gavage for 14 days), Group V (SLY + CP group; 100 mg/kg/day SLY by gavage for 14 days plus 30 mg/kg/day CP intraperitoneally starting from the seventh day) and Group VI (CUR + CP group; 100 mg/kg/day CUR by gavage for 14 days plus 30 mg/kg/day CP intraperitoneally starting from the seventh day). Biochemical, histopathological and immunohistochemical methods were utilised for evaluation of the cardiotoxicity.

Results

The result showed that an increase in heart MDA and DNA fragmentation levels were detected while significant decreases were seen in SOD levels in CP alone group when compared to the other groups. CP caused severe damage in the histopathological status of heart tissue including intersititial oedema, haemorrhage, degeneration and necrosis in muscle fibrils and perinuclear vacuolization. A significant increase in the percentage of TUNEL-positive cells and γH2AX protein expression was detected in the CP-treated group compared to the control and other treated groups. There was significant increase in the percentage of caspase 3-positive cells and decrease in the percentage of Bcl-2 positive cells in the CP group compared to the control group and other treated groups. However, a significant decrease in the percentage of cTnI and cTnT immunoreactivity was also observed in the CP-treated group compared to the control and other treated groups. In the groups in which SLY and CUR were administered concurrently with CP, biochemical parameters, histopathological and immunohistochemical results were found to be significantly lower than in the CP-only group.

Conclusions

These results lead to conclusion that the natural antioxidant SLY and CUR might have protective effects against CP-induced cardiotoxicity and oxidative stress in rats.

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水飞蓟素和姜黄素对环磷酰胺所致心脏毒性的保护作用

环磷酰胺(CP)是一种有效的抗癌药物;由于其明显的心脏毒性，其临床应用受到限制。目的探讨具有较强抗氧化作用的水飞蓟素(SLY)和姜黄素(CUR)对大剂量CP对大鼠心脏的保护作用。材料与方法选取成年Wistar白化雌性大鼠36只，随机分为6组。第一组(对照组;未给药)，第二组(CP组;每只动物腹腔注射30 mg/kg/天CP，连续7 d);100 mg/kg/天SLY灌胃14 d)， IV组(CUR组;100 mg/kg/天CUR灌胃14 d)， V组(SLY + CP组;SLY灌胃100 mg/kg/天，连续14天，第7天开始腹腔注射30 mg/kg/天CP)和VI组(CUR + CP组;100 mg/kg/day CUR灌胃14天，第7天开始腹腔注射30 mg/kg/day CP)。采用生物化学、组织病理学和免疫组织化学方法评价心脏毒性。结果与其他各组相比，CP单独治疗组心肌MDA和DNA片段水平升高，SOD水平明显降低。CP在心脏组织病理学状态下造成严重损害，包括间质水肿、出血、肌纤维变性和坏死以及核周空泡化。与对照组和其他处理组相比，cp处理组tunel阳性细胞百分比和γH2AX蛋白表达显著增加。与对照组和其他治疗组相比，CP组caspase 3阳性细胞百分比显著升高，Bcl-2阳性细胞百分比显著降低。然而，与对照组和其他治疗组相比，cp治疗组的cTnI和cTnT免疫反应性百分比也显著下降。在SLY和CUR同时给药CP组中，生化指标、组织病理学和免疫组织化学结果明显低于单独给药CP组。结论天然抗氧化剂SLY和CUR可能对cp诱导的大鼠心脏毒性和氧化应激具有保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental and Toxicologic Pathology 医学-病理学

CiteScore

2.08

自引率

0.00%

发文量

审稿时长

5.3 weeks

期刊介绍： Cessation. The international multidisciplinary journal is devoted to the publication of studies covering the whole range of experimental research on disease processes and toxicology including cell biological investigations. Its aim is to support progress in the interdisciplinary cooperation of researchers working in pathobiology, toxicology, and cell biology independent of the methods applied. During the past decades increasing attention has been paid to the importance of toxic influence in the pathogenesis of human and animal diseases. This is why Experimental and Toxicologic Pathology meets the urgent need for an interdisciplinary journal felt by a wide variety of experts in medicine and biology, including pathologists, toxicologists, biologists, physicians, veterinary surgeons, pharmacists, and pharmacologists working in academic, industrial or clinical institutions.