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Bisphenol A aggravates renal ischemia–reperfusion injury by disrupting mitochondrial homeostasis and N‐acetylcysteine mitigates the injurious outcomes
IUBMB Life ( IF 4.6 ) Pub Date : 2019-10-06 , DOI: 10.1002/iub.2175
Wachirasek Peerapanyasut 1 , Anongporn Kobroob 2 , Siripong Palee 3 , Nipon Chattipakorn 3 , Orawan Wongmekiat 1
Affiliation  

Exposure to bisphenol A (BPA), a chemical generally used in consumer products, becomes a global public health concern, as humans are increasingly exposed through their daily consuming activities. Renal ischemia–reperfusion (RIR) is the major cause of acute kidney injury with high prevalence and increased long‐term risks for multiple comorbidities and mortality. As the kidney is susceptible to these conditions, we explored whether the outcomes following the RIR episode could be influenced by BPA exposure, and investigated the therapeutic possibility by N‐acetylcysteine (NAC) including the mechanisms involved. Three groups of male Wistar rats were fed with vehicle, BPA 5, and 50 mg/kg, respectively, for five consecutive weeks then underwent the sham operation. Three other groups with identical treatment underwent bilateral renal IR induction (45‐min ischemia followed by 24‐hr reperfusion). An additional RIR group was treated with BPA 50 plus NAC 100 mg/kg. BPA‐exposed rats that encountered RIR episode showed dose‐dependent worsening of RIR injury as evidenced by augmentations of renal dysfunction and histopathological abnormalities, oxidative stress, apoptosis, mitochondrial functional impairment, mitochondrial dynamic, and mitophagy disproportion compared with the vehicle‐exposed RIR group. The NAC therapy considerably attenuated the exacerbated effects of BPA, which was associated with increased AMP‐activated protein kinase (AMPK), PGC‐1α, silent information regulator 3 or sirtuin 3 (SIRT3), and mitofusin 2 (MFN2) expressions but decreased Phosphorylated dynamin‐related protein 1 (p‐DRP1)/Dynamin‐related protein 1 (DRP1), PTEN‐induced putative kinase (PINK), and PARKIN expressions. These findings reveal the detrimental effect of repeated BPA exposure on the renal outcomes following the IR episode, and further demonstrate the protective efficacy of NAC by maintaining mitochondrial homeostasis, which is, partly, mediated through the AMPK‐PGC‐1α‐SIRT3 axis.

中文翻译:

双酚A通过破坏线粒体稳态加重肾缺血再灌注损伤,N-乙酰半胱氨酸减轻损伤结果

双酚 A (BPA) 是消费品中常用的一种化学物质,随着人类通过日常消费活动越来越多地接触到双酚 A (BPA),它已成为全球公共卫生问题。肾缺血再灌注(RIR)是急性肾损伤的主要原因,其患病率高,多种合并症和死亡率的长期风险增加。由于肾脏容易受到这些情况的影响,我们探讨了 RIR 发作后的结果是否会受到 BPA 暴露的影响,并研究了 N-乙酰半胱氨酸 (NAC) 的治疗可能性,包括所涉及的机制。三组雄性 Wistar 大鼠分别被喂以载体、BPA 5 和 50 mg/kg,连续五周,然后进行假手术。其他三个具有相同治疗的组进行了双侧肾脏 IR 诱导(45 分钟缺血,然后 24 小时再灌注)。另一个 RIR 组用 BPA 50 加 NAC 100 mg/kg 治疗。与暴露于载体的 RIR 组相比,暴露于 BPA 的大鼠表现出剂量依赖性的 RIR 损伤恶化,这表现为肾功能障碍和组织病理学异常、氧化应激、细胞凋亡、线粒体功能障碍、线粒体动力学和线粒体自噬不成比例的增加. NAC 治疗大大减弱了 BPA 的恶化作用,这与 AMP 活化蛋白激酶 (AMPK)、PGC-1α、沉默信息调节剂 3 或 Sirtuin 3 (SIRT3) 的增加有关,和线粒体融合蛋白 2 (MFN2) 表达,但降低磷酸化动力蛋白相关蛋白 1 (p-DRP1)/动力蛋白相关蛋白 1 (DRP1)、PTEN 诱导的推定激酶 (PINK) 和 PARKIN 表达。这些发现揭示了重复 BPA 暴露对 IR 发作后肾脏结局的不利影响,并进一步证明了 NAC 通过维持线粒体稳态的保护功效,这部分是通过 AMPK-PGC-1α-SIRT3 轴介导的。
更新日期:2019-10-06
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