Institute for Agri-Food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, Shanghai 201403, China.
College of Food Science and Engineering, Shandong Agricultural University, Tai'an, Shandong 271018, China.
Ecotoxicol Environ Saf. 2021 Jan 15;208:111638. doi: 10.1016/j.ecoenv.2020.111638. Epub 2020 Nov 16.
The flame retardant decabrominated diphenyl ether (BDE-209) is a widely used chemical in a variety of products and exists extensively in the environment. BDE-209 has been reported to induce kidney injury and dysfunction. However, the causes and mechanisms of its nephrotoxicity are still under investigation. In this study, 150 male broilers were exposed to BDE-209 concentrations of 0, 0.004, 0.04, 0.4, 4.0 g/kg for 42 days. The relative kidney weight, histopathology, markers of renal injury, oxidative stress, inflammation, apoptosis and the expression of MAPK signaling pathways-related proteins were assessed. The results showed that the concentrations of blood urea nitrogen (BUN), creatinine (CRE) and the neutrophil gelatinase-associated lipocalin (NGAL), significantly increased after exposure to BDE-209 with the doses more than 0.04 g/kg. Similarly, severe damage of renal morphology was observed, including atrophy and necrosis of glomeruli, and swelling and granular degeneration of the renal tubular epithelium. In the renal homogenates, the oxidative stress was evidenced by the elevated concentrations of MDA and NO, and decreased levels of GSH-Px, GSH and SOD. Due to the inflammatory response, the level of NF-κB and the pro-inflammatory cytokines TNF-α, IL-1β, IL-18 were remarkably upregulated, while the content of the anti-inflammatory cytokine IL-10 decreased. Additionally, the apoptotic analysis showed notable upregulations of Bax/Bcl-2 ratio, the relative expression of p-ERK1/2 and p-JNK1/2, and the expression of Bax, cytochrome c and caspase 3. The present study indicates that BDE-209 exposure can cause nephrotoxicity in broilers through oxidative stress and inflammation, which activate the phosphorylation of key proteins of the MAPK signaling pathways, and subsequently induce mitochondria-mediated kidney apoptosis.
十溴联苯醚（BDE-209）是一种广泛应用于各种产品的阻燃剂，在环境中广泛存在。BDE-209 已被报道会引起肾脏损伤和功能障碍。然而，其肾毒性的原因和机制仍在研究中。在这项研究中，将 150 只雄性肉鸡暴露于 0、0.004、0.04、0.4 和 4.0 g/kg 的 BDE-209 浓度下 42 天。评估了相对肾脏重量、组织病理学、肾脏损伤标志物、氧化应激、炎症、细胞凋亡以及 MAPK 信号通路相关蛋白的表达。结果表明，暴露于 BDE-209 后，血液尿素氮（BUN）、肌酐（CRE）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）的浓度显著升高，且剂量大于 0.04 g/kg。同样，观察到严重的肾脏形态损伤，包括肾小球萎缩和坏死，以及肾小管上皮细胞肿胀和颗粒状变性。在肾匀浆中，通过升高的 MDA 和 NO 浓度以及降低的 GSH-Px、GSH 和 SOD 水平证实了氧化应激。由于炎症反应，NF-κB 水平和促炎细胞因子 TNF-α、IL-1β、IL-18 的水平显著上调，而抗炎细胞因子 IL-10 的含量降低。此外，凋亡分析显示 Bax/Bcl-2 比值、p-ERK1/2 和 p-JNK1/2 的相对表达以及 Bax、细胞色素 c 和 caspase 3 的表达显著上调。本研究表明，BDE-209 暴露可通过氧化应激和炎症导致肉鸡发生肾毒性，进而激活 MAPK 信号通路关键蛋白的磷酸化，随后诱导线粒体介导的肾脏细胞凋亡。
