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Bromoacetic acid causes oxidative stress and uric acid metabolism dysfunction via disturbing mitochondrial function and Nrf2 pathway in chicken kidney
Environmental Toxicology ( IF 4.4 ) Pub Date : 2022-08-26 , DOI: 10.1002/tox.23647
Yuting Wu 1 , Jiwen Liu 1 , Shuhui Liu 1 , Wentao Fan 1 , Chenchen Ding 1 , Zhangshan Gao 1 , Zhihui Tang 1 , Yan Luo 2 , Xizhi Shi 3 , Lei Tan 2 , Suquan Song 1
Affiliation  

Since the outbreak of COVID-19, widespread utilization of disinfectants has led to a tremendous increase in the generation of disinfection byproducts worldwide. Bromoacetic acid (BAA), one of the common disinfection byproducts in the environment, has triggered public concern because of its adverse effects on urinary system in mammals. Nevertheless, the BAA-induced nephrotoxicity and potential mechanism in birds still remains obscure. According to the detected content in the Taihu Lake Basin, the model of BAA exposure in chicken was established at doses of 0, 3, 300, 3000 μg/L for 4 weeks. Our results indicated that BAA exposure caused kidney swelling and structural disarrangement. BAA led to disorder in renal function (CRE, BUN, UA) and increased apoptosis (Bax, Bcl-2, caspase3). BAA suppressed the expression of mitochondrial biogenesis genes (PGC-1α, Nrf1, TFAM) and OXPHOS complex I genes (ND1, ND2, ND3, ND4, ND4L, ND5, ND6). Subsequently, BAA destroyed the expression of Nrf2 antioxidant reaction genes (Nrf2, Keap1, HO-1, NQO1, GCLM, GCLC). Furthermore, renal oxidative damage led to disorder in uric acid metabolism genes (Mrp2, Mrp4, Bcrp, OAT1, OAT2, OAT3) and exacerbated destruction in renal function. Overall, our study provided insights into the potential mechanism of BAA-induced nephrotoxicity, which were important for the clinical monitoring and prevention of BAA.

中文翻译:

溴乙酸通过干扰鸡肾脏线粒体功能和Nrf2通路引起氧化应激和尿酸代谢障碍

自 COVID-19 爆发以来,消毒剂的广泛使用导致全球消毒副产物的产生量大幅增加。溴乙酸(BAA)是环境中常见的消毒副产物之一,因其对哺乳动物泌尿系统的不良影响而引起公众关注。然而,BAA 诱导的鸟类肾毒性和潜在机制仍然不清楚。根据太湖流域检出物含量,建立鸡BAA暴露模型,剂量为0、3、300、3000μg/L,持续4周。我们的结果表明,暴露于 BAA 会导致肾脏肿胀和结构紊乱。BAA 导致肾功能紊乱(CRE、BUN、UA)和细胞凋亡增加(Bax、Bcl-2、caspase3)。BAA 抑制线粒体生物合成基因(PGC-1α、Nrf1、TFAM)和 OXPHOS 复合物 I 基因(ND1、ND2、ND3、ND4、ND4L、ND5、ND6)的表达。随后,BAA破坏了Nrf2抗氧化反应基因(Nrf2、Keap1、HO-1、NQO1、GCLM、GCLC)的表达。此外,肾脏氧化损伤导致尿酸代谢基因(Mrp2、Mrp4、Bcrp、OAT1、OAT2、OAT3)紊乱,加剧肾功能破坏。总的来说,我们的研究提供了对 BAA 诱导肾毒性的潜在机制的见解,这对于 BAA 的临床监测和预防非常重要。肾脏氧化损伤导致尿酸代谢基因(Mrp2、Mrp4、Bcrp、OAT1、OAT2、OAT3)紊乱,加剧肾功能破坏。总的来说,我们的研究提供了对 BAA 诱导肾毒性的潜在机制的见解,这对于 BAA 的临床监测和预防非常重要。肾脏氧化损伤导致尿酸代谢基因(Mrp2、Mrp4、Bcrp、OAT1、OAT2、OAT3)紊乱,加剧肾功能破坏。总的来说,我们的研究提供了对 BAA 诱导肾毒性的潜在机制的见解,这对于 BAA 的临床监测和预防非常重要。
更新日期:2022-08-26
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