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Curcumin alleviates colistin-induced nephrotoxicity and neurotoxicity in rats via attenuation of oxidative stress, inflammation and apoptosis
Chemico-Biological Interactions ( IF 5.1 ) Pub Date : 2018-08-20 , DOI: 10.1016/j.cbi.2018.08.012
Nagah E. Edrees , Azza A.A. Galal , Aliaa R. Abdel Monaem , Rasha R. Beheiry , Mohamed M.M. Metwally

Colistin is an effective antibiotic against multidrug-resistant (MDR) gram-negative bacterial infections; however, nephrotoxic and neurotoxic effects are fundamental dose-limiting factors for this treatment. This study was conducted to assess the potential protective effects of curcumin, a phenolic constituent of turmeric, against colistin-induced nephrotoxicity and neurotoxicity, and the possible mechanisms underlying any effect. Twenty-four adult male albino rats were randomly classified into 4 equal groups; the control group (orally received saline solution), the curcumin-treated group (orally administered 200 mg curcumin/kg/day), the colistin-treated group (IP administered 300,000 IU colistin/kg/day) and the concurrent group (orally received 200 mg curcumin/kg/day concurrently with colistin injection); all rats were treated for 6 successive days. Colistin administration significantly increased serum creatinine, urea and uric acid levels as well as brain gamma butyric acid (GABA) concentrations. In renal and brain tissues, colistin significantly increased malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and caspase-3 expression levels. In addition, colistin significantly decreased catalase (CAT), glutathione (GSH), and B-cell lymphoma 2 (Bcl-2) expressions. Curcumin administration in colistin-treated rats partially restored each of these altered biochemical, antioxidant, inflammatory and apoptotic markers. Histopathological changes in renal and brain tissues were also alleviated by curcumin co-treatment. Our study reveals a critical role of oxidative damage, inflammation and apoptosis in colistin-induced nephrotoxicity and neurotoxicity and showed that they were markedly ameliorated by curcumin co-administration. Therefore, curcumin could represent a promising agent for prevention of colistin-induced nephrotoxicity and neurotoxicity.



中文翻译:

姜黄素通过减轻氧化应激,炎症和细胞凋亡减轻粘菌素诱导的大鼠肾毒性和神经毒性

Colistin是一种有效的抗多药耐药(MDR)革兰氏阴性细菌感染的抗生素。然而,肾毒性和神经毒性作用是该治疗的基本剂量限制因素。进行这项研究的目的是评估姜黄素(姜黄的酚类成分)对大肠菌素诱导的肾毒性和神经毒性的潜在保护作用,以及可能产生任何作用的机制。将24只成年雄性白化病大鼠随机分为4组,每组4只。对照组(口服盐溶液),姜黄素治疗组(口服200 mg姜黄素/ kg /天),大肠菌素治疗组(腹膜内给药300,000 IU大肠杆菌素/ kg /天)和同时组(口服)粘菌素注射的同时200 mg姜黄素/ kg /天); 所有大鼠连续治疗6天。Colistin的给药显着增加了血清肌酐,尿素和尿酸水平以及脑γ丁酸(GABA)浓度。在肾和脑组织中,粘菌素可显着增加丙二醛(MDA),一氧化氮(NO),肿瘤坏死因子-α(TNF-α),白介素6(IL-6)和caspase-3表达水平。此外,粘菌素可显着降低过氧化氢酶(CAT),谷胱甘肽(GSH)和B细胞淋巴瘤2(Bcl-2)的表达。在经粘菌素处理的大鼠中施用姜黄素可部分恢复这些改变的生化,抗氧化剂,炎性和凋亡标记物中的每一种。姜黄素联合治疗也减轻了肾脏和脑组织的组织病理学变化。我们的研究揭示了氧化损伤的关键作用,粘菌素诱导的肾毒性和神经毒性引起的炎症和细胞凋亡,并显示姜黄素共同给药可明显改善它们。因此,姜黄素可能是预防大肠菌素引起的肾毒性和神经毒性的有前途的药物。

更新日期:2018-08-20
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