Comparative nephroprotective effects of curcumin and etoricoxib against cisplatin-induced acute kidney injury in rats
Comparative nephroprotective effects of curcumin and etoricoxib against cisplatin-induced acute kidney injury in rats
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DOI：
10.1016/j.acthis.2020.151534
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发表时间：
2020-05-01
影响因子：
2.5
通讯作者：
Taha, Reham Ismail
中科院分区：
文献类型：
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作者：
Abd El-Kader, Marwa;Taha, Reham Ismail
目的：顺铂虽然是一种有效的化疗药物，但肾毒性仍是其威胁生命的主要副作用。为探讨和比较姜黄素(Cur)和依托昔布(ETB)对顺铂肾毒性的保护作用。材料与方法：成年雌性大鼠36只，随机分为6组：对照组(C组)、顺铂(C组)(7.5 mg/kg)、姜黄素(200 mg/kg/d)、依托昔布(10 mg/kg/d)。V组(CIS+Cur)和VI组(CIS+ETB)给予姜黄素(200 mg/kg/d)或依托昔布(10 mg/kg/d)灌胃，连续7d。第4天，末次给予姜黄素或依托昔布后1h，单次注射顺铂7.5 mg/kg。结果：姜黄素可显著降低顺铂所致大鼠血清肌酐和尿素氮(BUN)的升高，逆转氧化应激标志物谷胱甘肽(GSH)和丙二醛(MDA)的升高。逆转录聚合酶链式反应检测肾组织iNOS和Bax免疫组织化学反应及肿瘤坏死因子-α和半胱氨酸天冬氨酸氨基转移酶3基因的表达，证明Cur联合治疗可抑制炎症和细胞凋亡反应。据我们所知，这是首次探讨ETB对顺铂所致肾毒性的影响。尽管ETB降低了上述炎症和凋亡标志物，但其作用弱于Cur。ETB不能改变肾组织肌酐、BUN、GSH和MDA的紊乱水平。结论：Cur对顺铂所致的肾毒性具有良好的肾脏保护作用。建议进一步研究是否认可ETB在顺铂所致肾毒性中的保护作用。
Objective: Although cisplatin (CIS) acts as potent chemotherapy, nephrotoxicity still its major life-threatening side effect. The purpose of this study was to discuss and compare the renoprotective effects of curcumin (CUR) and etoricoxib (ETB) against CIS-induced nephrotoxicity.Materials & methods: Thirty six adult female rats were divided equally into 6 groups: Group I (control), Group II (CIS) received cisplatin (7.5 mg/kg i.p), Group III (CUR) and group IV (ETB) received curcumin (200 mg/kg/day) or etoricoxib (10 mg/kg/day) respectively via gavage for seven continuous days. Group V (CIS + CUR) and Group VI (CIS + ETB) received curcumin (200 mg/kg/day) or etoricoxib (10 mg/kg/day) via gavage for seven continuous days. On the 4th day, the rats received cisplatin (7.5 mg/kg i.p) as a single injection 1 h after last curcumin or etoricoxib administration. At the assigned time, blood and tissue samples were collected for biochemical, histochemical, histopathological, immunohistochemical, and RT-PCR gene expression studies.Results: Curcumin administration significantly decreased CIS-induced elevation of serum creatinine and blood urea nitrogen (BUN), and reversed oxidative stress markers; glutathione (GSH) and malondialdehyde (MDA) to control level. Suppression of inflammatory and apoptotic responses by CUR co-treatment was evidenced by decreased iNOS and BAX immunohistochemical reactions, and TNF-alpha and Caspase3 gene expressions which were detected by RT-PCR in kidney tissues. To our knowledge, this is the first time to discuss the effect of ETB on CIS induced nephrotoxicity. Although ETB reduced the previously mentioned inflammatory and apoptotic markers, its effect was less than that of CUR. Administration of ETB couldn't modify the disturbed levels of creatinine, BUN, GSH, and MDA.Conclusion: In conclusion, CUR provided a promising renoprotective effect against CIS induced nephrotoxicity. Further studies are recommended to approve or disapprove the protective role of ETB in CIS induced nephrotoxicity.