Rottlerin, a polyphenolic compound from the fruits of Mallotus phillipensis (Lam.) Mull.Arg., impedes oxalate/calcium oxalate induced pathways of oxidative stress in male wistar rats
Rottlerin, a polyphenolic compound from the fruits of Mallotus phillipensis (Lam.) Mull.Arg., impedes oxalate/calcium oxalate induced pathways of oxidative stress in male wistar rats
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DOI：
10.1016/j.phymed.2016.06.005
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发表时间：
2016-09-15
期刊：
影响因子：
7.9
通讯作者：
Singla, Surinder
中科院分区：
文献类型：
--
作者：
Chhiber, Nirlep;Kaur, Tanzeer;Singla, Surinder
背景：已知草酸和/或草酸钙可诱导自由基产生，继而导致肾上皮损伤。氧化应激和线粒体功能障碍已成为管理草酸所致肾损伤的新靶点。假设：植物产品和抗氧化剂在预防结石性疾病方面得到了极大的关注。Rottlerin是从海棠Mallotus Phillipensis(Lam.)已经显示出清除自由基、抗氧化活性，并被报道干扰导致炎症和细胞凋亡的信号通路。方法：给雄性Wistar大鼠饮水中加入0.4%乙二醇液和1%氯化铵溶液，连续9天建立高草酸尿症模型。同时给予罗特林1 mg/kg/d和高草酸尿剂。结果：0.4%乙二醇组和1%氯化铵组大鼠出现高草酸尿、氧化应激和线粒体损伤。Rottlerin治疗降低了NADPH氧化酶的活性，防止了线粒体功能障碍，并维持了抗氧化环境。罗特林还能改善高草酸血症大鼠的肾功能、组织完整性和降低尿液结晶负荷。结论：罗特林能明显减轻高草酸血症的后果，其作用机制可能与其自身具有清除自由基的能力和阻断结石形成过程中的信号通路有关。(C)2016年爱思唯尔股份有限公司。版权所有。
Background: Oxalate and/or calcium oxalate, is known to induce free radical production, subsequently leading to renal epithelial injury. Oxidative stress and mitochondrial dysfunction have emerged as new targets for managing oxalate induced renal injury.Hypothesis: Plant products and antioxidants have gained tremendous attention in the prevention of lithiatic disease. Rottlerin, a polyphenolic compound from the fruits of Mallotus phillipensis (Lam.) Mull.Arg., has shown free radical scavenging, antioxidant activity and has been reported to interfere in signaling pathways leading to inflammation and apoptosis. In this study, the potential role of rottlerin, in rats exposed to hyperoxaluric environment was explored.Methods: Hyperoxaluria was induced by administering 0.4% ethylene glycol and 1% ammonium chloride in drinking water to male wistar rats for 9 days. Rottlerin was administered intraperitoneally at 1 mg/kg/day along with the hyperoxaluric agent. Prophylactic efficacy of rottlerin to diminish hyperoxaluria induced renal dysfunctionality and crystal load was examined along with its effect on free radicals generating pathways in hyperoxaluric rats.Results: 0.4% ethylene glycol and 1% ammonium chloride led to induction of hyperoxaluria, oxiadtive stress and mitochondrial damage in rats. Rottlerin treatment reduced NADPH oxidase activity, prevented mitochondrial dysfunction and maintained antioxidant environment. It also refurbished renal functioning, tissue integrity and diminished urinary crystal load in hyperoxaluric rats treated with rottlerin.Conclusions: Thus, the present investigation suggests that rottlerin evidently reduced hyperoxaluric consequences and the probable mechanism of action of this drug could be attributed to its ability to quench free radicals by itself and interrupting signaling pathways involved in pathogenesis of stone formation. (C) 2016 Elsevier GmbH. All rights reserved.