Kumar Parveen, Sulakhiya Kunjbihari, Barua Chandana C, Mundhe Nitin
Laboratory of Molecular Pharmacology and Toxicology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India.
Department of Pharmacology, Pandit Jawahar Lal Nehru Government Medical College Chamba, Chamba, 176324, Himachal Pradesh, India.
Mol Cell Biochem. 2017 Jul;431(1-2):113-122. doi: 10.1007/s11010-017-2981-5. Epub 2017 Mar 3.
Cisplatin is a regularly employed effective chemotherapeutic agent for the treatment of many types of cancer. The main drawback of cisplatin treatment is kidney toxicity which affects 25-35% of treated patients. Many mechanisms are believed to be involved in this kidney damage, but inflammation plays a significant role in this event. Curcumin is a polyphenol and has antioxidant and anti-inflammatory effects. The purpose of this study was to determine the protective effects of curcumin on cisplatin-induced nephrotoxicity. Female rats were randomly divided into 5 groups: control, curcumin, cisplatin, curcumin plus cisplatin (pre-treatment group) and cisplatin plus curcumin (post-treatment group). Rats were given cisplatin (7.5 mg/kg body weight) with or without curcumin treatment (120 mg/kg body weight). Blood urea nitrogen (BUN), creatinine, albumin, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL-10 expressions and histological changes were determined on the 5th day after cisplatin injection. Acute kidney damage was evident by increased BUN and creatinine levels. In addition, cisplatin showed a marked pro-inflammatory response as revealed by a significant increase in the tissue levels of TNF-α, IL-6, IL-8 and decrease in the IL-10 level. Pre-treatment of curcumin reduced cisplatin-induced nephrotoxicity which was clearly evident from the reduced BUN, creatinine, TNF-α, IL-6 and IL-8 levels and increased albumin and IL-10 levels. Additionally, these findings were also supported by histopathology of the kidneys. In contrast, post-treatment of curcumin failed to cut down the expression of inflammatory markers substantially and also neglected to increase the expression of IL-10. The disparity in the action of curcumin after pre- and post-treatment with cisplatin-induced nephrotoxicity was due to the inability of post-treatment to reduce TNF-α & IL-6, besides to show a concurrent rise in IL-10 expression in renal tissues.
顺铂是一种常用于治疗多种癌症的有效化疗药物。顺铂治疗的主要缺点是肾毒性，25%至35%的接受治疗的患者会受到影响。人们认为许多机制都与这种肾损伤有关，但炎症在这一过程中起着重要作用。姜黄素是一种多酚，具有抗氧化和抗炎作用。本研究的目的是确定姜黄素对顺铂诱导的肾毒性的保护作用。雌性大鼠被随机分为5组：对照组、姜黄素组、顺铂组、姜黄素加顺铂（预处理组）和顺铂加姜黄素（后处理组）。给大鼠注射顺铂（7.5毫克/千克体重），同时或不同时给予姜黄素治疗（120毫克/千克体重）。在注射顺铂后第5天测定血尿素氮（BUN）、肌酐、白蛋白、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-6、IL-8、IL-10的表达以及组织学变化。BUN和肌酐水平升高表明急性肾损伤明显。此外，顺铂显示出明显的促炎反应，TNF-α、IL-6、IL-8的组织水平显著升高，IL-10水平降低。姜黄素预处理降低了顺铂诱导的肾毒性，这从降低的BUN、肌酐、TNF-α、IL-6和IL-8水平以及升高的白蛋白和IL-10水平中明显可见。此外，这些发现也得到了肾脏组织病理学的支持。相比之下，姜黄素后处理未能大幅降低炎症标志物的表达，也未能增加IL-10的表达。姜黄素在顺铂诱导的肾毒性预处理和后处理后的作用差异是由于后处理无法降低TNF-α和IL-6，此外也未能使肾组织中IL-10表达同时升高。
