Elsherbiny Nehal M, Eladl Mohamed A, Al-Gayyar Mohammed M H
Department of Clinical Biochemistry, Faculty of Pharmacy, University of Mansoura, 35516, Egypt.
Department of Anatomy & Embryology, Faculty of Medicine, University of Mansoura, 35516, Egypt; Faculty of Medicine, Sharjah University, Sharjah, United Arab Emirates.
Cytokine. 2016 Jan;77:26-34. doi: 10.1016/j.cyto.2015.10.010. Epub 2015 Oct 27.
Cisplatin is the first platinum-containing anti-cancer drugs. Cisplatin notable side effect of nephrotoxicity limits its use in clinic. Meanwhile, arjunolic acid possesses anti-inflammatory properties and plays protective roles against chemically induced organ pathophysiology. This study was conducted to find out whether arjunolic acid could attenuate kidney damage in rats, and to elucidate its possible mechanism of action. Fifty rats were treated with cisplatin (10mg/kg) in the presence/absence of 100 or 250mg/kg arjunolic acid. Arjunolic acid is given 1h after cisplatin. Morphological changes were assessed in kidney sections stained with Hematoxylin/Eosin and Masson Trichrome. Kidney samples were used for measurements of transforming growth factor (TGF)-β1 and its type 1 receptor (TGF-βR1), tumor necrosis factor (TNF)-α and interleukin (IL)-1β by ELISA. Gene expression NFκB was determined by real time-PCR. Kidney tissue apoptosis was assessed by measuring the activities of caspase-3/8/9. The renal protective effect of arjunolic acid was confirmed by approximately normal appearance of renal tissue and the relatively unaffected serum creatinine and urea levels. Furthermore, arjunolic acid showed dose dependent reduction in cisplatin-induced elevation in renal levels of TGF-βR1, TGF-β1, TNF-α, IL-1β and caspases. These findings demonstrated that arjunolic acid attenuates cisplatin nephrotoxicity either indirectly by enhancing body antioxidant activity or directly through several mechanisms, including inhibition of pro-inflammatory cytokines, blocking activation of TGF-β1, and anti-apoptotic effects.
顺铂是第一种含铂抗癌药物。顺铂显著的肾毒性副作用限制了其在临床上的应用。同时，阿朱诺酸具有抗炎特性，并对化学诱导的器官病理生理学发挥保护作用。本研究旨在探究阿朱诺酸是否能减轻大鼠肾脏损伤，并阐明其可能的作用机制。五十只大鼠在有/无100或250mg/kg阿朱诺酸的情况下接受顺铂（10mg/kg）治疗。顺铂给药1小时后给予阿朱诺酸。用苏木精/伊红和Masson三色染色法评估肾脏切片的形态学变化。肾脏样本用于通过酶联免疫吸附测定法测量转化生长因子（TGF）-β1及其1型受体（TGF-βR1）、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β。通过实时聚合酶链反应测定核因子κB（NFκB）的基因表达。通过测量半胱天冬酶-3/8/9的活性评估肾脏组织凋亡。阿朱诺酸的肾脏保护作用通过肾脏组织外观大致正常以及血清肌酐和尿素水平相对未受影响得到证实。此外，阿朱诺酸显示出剂量依赖性地降低顺铂诱导的肾脏中TGF-βR1、TGF-β1、TNF-α、IL-1β和半胱天冬酶水平的升高。这些发现表明，阿朱诺酸通过增强机体抗氧化活性间接减轻顺铂肾毒性，或直接通过多种机制减轻，包括抑制促炎细胞因子、阻断TGF-β1的激活以及抗凋亡作用。
