Polybrominated diphenyl ethers (PBDEs) exist in aquatic environments with nephrotoxicity to non-target aquatic species. Melatonin (MT) exhibits an inhibitory effect of oxidative stress and apoptosis in various diseases. 2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47) is the main homolog of PBDE samples. Therefore, we investigated the toxic mechanism of BDE-47 and the alleviation effect of MT, the ctenopharyngodon idellus kidney (CIK) cells were treated with BDE-47 (100 μM) and/or MT (60 μM) for 24 h. Firstly, BDE-47 exposure could inhibit oxidative stress-related antioxidant enzymes (T-AOC, SOD, CAT and GPx) and increase the content of malondialdehyde (MDA) to cause oxidative stress. Secondly, BDE-47 enhanced mitochondrial division and inhibited fusion to induce mitochondrial membrane potential in CIK cells. BDE-47 enhanced the mRNA and protein levels of mitochondrial-pathway apoptosis related genes (Cas 3, Cyt-c, and BAX). Thirdly, BDE-47 treatment decreased the expression levels of mitochondrial-related regulatory factors AMPK-Sirt1-PGC-1α signal pathway. Intriguingly, BDE-47-induced oxidative stress, mitochondrial pathway apoptosis and mitochondrial dynamics disorder could be alleviated by MT treatment. Overall, we concluded that MT could relieve BDE-47-induced oxidative stress, mitochondrial dysfunction and apoptosis through the AMPK-Sirt1-PGC-1α axis. These results enrich the mechanisms of BDE-47 poisoning and reveal that MT treatment may be a potential strategy for solving BDE-47 poisoning.

多溴联苯醚 (PBDEs) 存在于水生环境中，对非目标水生物种具有肾毒性。褪黑激素 (MT) 在各种疾病中表现出对氧化应激和细胞凋亡的抑制作用。2, 2', 4, 4'-四溴二苯醚 (BDE-47) 是 PBDE 样品的主要同系物。因此，我们研究了 BDE-47 的毒性机制和 MT、 ctenopharyngodon idellus的缓解作用。用 BDE-47 (100 μM) 和/或 MT (60 μM) 处理肾 (CIK) 细胞 24 小时。首先，BDE-47 暴露可以抑制氧化应激相关的抗氧化酶（T-AOC、SOD、CAT 和 GPx），增加丙二醛（MDA）的含量，引起氧化应激。其次，BDE-47 在 CIK 细胞中增强线粒体分裂并抑制融合以诱导线粒体膜电位。BDE-47 增强了线粒体途径凋亡相关基因（Cas 3、Cyt-c 和 BAX）的 mRNA 和蛋白质水平。第三，BDE-47 处理降低了线粒体相关调节因子 AMPK-Sirt1-PGC-1α 信号通路的表达水平。有趣的是，MT 治疗可以缓解 BDE-47 诱导的氧化应激、线粒体途径凋亡和线粒体动力学紊乱。全面的，我们得出结论，MT 可以通过 AMPK-Sirt1-PGC-1α 轴缓解 BDE-47 诱导的氧化应激、线粒体功能障碍和细胞凋亡。这些结果丰富了 BDE-47 中毒的机制，并表明 MT 治疗可能是解决 BDE-47 中毒的潜在策略。