a Laboratory of Pharmacology , National Institute of Pharmaceutical Education and Research , Guwahati , Assam , India.
b Department of Pharmacology , Pandit Jawaharlal Nehru Government Medical College Chamba , Chamba , Himachal Pradesh , India.
Immunopharmacol Immunotoxicol. 2019 Feb;41(1):68-75. doi: 10.1080/08923973.2018.1547741. Epub 2019 Jan 3.
Nephrotoxicity is a highly manifested complication in cancer patients undergoing cisplatin therapy. Oxidative stress, nitrosative stress, and inflammation are the major patho-mechanisms of cisplatin-induced nephrotoxicity. The purpose of this study was to determine the protective effect of pretreatment and post-treatment of nordihydroguaiarectic acid (NDGA) on cisplatin-induced nephrotoxicity. Cisplatin-induced renal damage was accessed by biochemical estimation of nephrotoxicity markers, oxidative and nitrosative stress whereas inflammatory markers were accessed by ELISA technique. Cisplatin administration had resulted in renal injury associated with oxidative stress, nitrosative stress as evident by increased MDA, ROS, and nitrite level with decreased antioxidants such as SOD, catalase and, glutathione. Furthermore, cisplatin treated animals exhibited a noticeable pro-inflammatory response with the substantial increase in renal levels of TNF-α, IL-1β, and IL-6 and decrease in the renal level of IL-10. NDGA pretreatment did not lead to significantly rise in oxidative stress, nitrosative stress, and inflammation along with restored the level of IL-10 in the kidney and preserved renal function. Moreover, NDGA post-treatment also presented nephroprotective effects, but the effects were not as positive as compared to NDGA pretreatment. In conclusion, these results indicate that NDGA pretreatment is renoprotective while on the other hand NDGA post-treatment is not so effective in cisplatin-induced nephrotoxicity.
肾毒性是癌症患者接受顺铂治疗时表现明显的并发症。氧化应激、硝化应激和炎症是顺铂诱导肾毒性的主要病理机制。本研究旨在确定预处理和后处理去甲二氢愈创木酸（NDGA）对顺铂诱导的肾毒性的保护作用。通过生化评估肾毒性标志物、氧化应激和硝化应激来评估顺铂诱导的肾损伤，而通过 ELISA 技术评估炎症标志物。顺铂给药导致与氧化应激、硝化应激相关的肾损伤，表现为 MDA、ROS 和亚硝酸盐水平增加，而 SOD、过氧化氢酶和谷胱甘肽等抗氧化剂水平降低。此外，顺铂处理的动物表现出明显的促炎反应，肾组织中 TNF-α、IL-1β 和 IL-6 水平显著增加，而 IL-10 水平降低。NDGA 预处理不会显著增加氧化应激、硝化应激和炎症，同时恢复肾脏中 IL-10 的水平并维持肾功能。此外，NDGA 后处理也表现出肾保护作用，但效果不如 NDGA 预处理。总之，这些结果表明，NDGA 预处理具有肾保护作用，而另一方面，NDGA 后处理在顺铂诱导的肾毒性中效果不那么显著。
