Anatomy and Embryology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Acta Histochem. 2020 May;122(4):151534. doi: 10.1016/j.acthis.2020.151534. Epub 2020 Mar 6.
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.
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-α 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.
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.
顺铂（cisplatin，CIS）作为一种有效的化疗药物，但仍存在肾毒性这一主要的致命副作用。本研究旨在探讨和比较姜黄素（curcumin，CUR）和依托考昔（etoricoxib，ETB）对顺铂诱导的肾毒性的保护作用。
36 只成年雌性大鼠平均分为 6 组：I 组（对照组）；II 组（CIS 组）腹腔注射顺铂（7.5mg/kg）；III 组（CUR 组）和 IV 组（ETB 组）分别灌胃给予姜黄素（200mg/kg/天）和依托考昔（10mg/kg/天），连续 7 天；V 组（CIS+CUR 组）和 VI 组（CIS+ETB 组）在连续 7 天灌胃给予姜黄素（200mg/kg/天）和依托考昔（10mg/kg/天）后，于第 4 天腹腔注射顺铂（7.5mg/kg）。在指定时间点采集血样和组织样本，进行生化、组织化学、组织病理学、免疫组化和 RT-PCR 基因表达研究。
姜黄素的给予可显著降低顺铂诱导的血清肌酐和血尿素氮（BUN）升高，并将氧化应激标志物谷胱甘肽（glutathione，GSH）和丙二醛（malondialdehyde，MDA）恢复至正常水平。姜黄素联合治疗可抑制诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）和 BAX 的免疫组化反应，降低肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和半胱氨酸天冬氨酸蛋白酶 3（caspase3，Caspase3）的基因表达，从而抑制炎症和细胞凋亡反应。据我们所知，这是首次探讨依托考昔对顺铂诱导的肾毒性的影响。虽然依托考昔降低了上述炎症和凋亡标志物，但效果不如姜黄素。依托考昔的给予并不能改变肌酐、BUN、GSH 和 MDA 的紊乱水平。
综上所述，姜黄素对顺铂诱导的肾毒性具有潜在的保护作用。需要进一步的研究来证实或否定依托考昔在顺铂诱导的肾毒性中的保护作用。
