Gan Rao, Liu Haiyan, Wu Shaofeng, Huang Riming, Tang Zhaoxin, Zhang Ning, Hu Lianmei
College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou, 510642, China.
Biol Trace Elem Res. 2023 May;201(5):2503-2511. doi: 10.1007/s12011-022-03321-4. Epub 2022 Jun 23.
Arsenic (As) as a neurotoxic environmental pollutant has attracted extensive attention. Curcumin (Cur) is a natural antioxidant that shows an excellent protective effect against arsenic trioxide (ATO)-induced toxicity in many animal organs. However, the mechanism of Cur against ATO-induced hypothalamic toxicity in ducks has not yet been fully elucidated. Here, ducks were treated with ATO and/or Cur during 28 days; the results showed that ATO exposure induced growth retardation, messy feathers, and abnormal posture in ducks. Moreover, ATO caused neuron vacuolar degeneration and disintegration in the hypothalamus of ducks. Simultaneously, ATO induced blood-brain barrier damage, downregulated the expression of ZO-1, Occludin, and mediated NF-κB activation, resulting in an increase in inflammatory factors (TLR-4, NF-κB, TNF-α, IL-2, and IL-6). Furthermore, ATO increased the production of pyroptosis-related factors (Caspase-1, IL-18, IL-1), exacerbating the inflammatory damage through NLRP3-mediated inflammasome activation. Cur, on the other hand, exerted excellent inhibitory effects on inflammation and pyroptosis. In summary, our study revealed that ATO triggered inflammation and pyroptosis by modulating NF-κB/NLRP3 signaling pathways in the hypothalamus of ducks, and Cur can alleviate inflammation and pyroptosis caused by ATO. Therefore, as a plant extract, Cur has the potential to prevent and cure ATO-induced hypothalamus toxicity.
砷（As）作为一种具有神经毒性的环境污染物已引起广泛关注。姜黄素（Cur）是一种天然抗氧化剂，在许多动物器官中对三氧化二砷（ATO）诱导的毒性表现出优异的保护作用。然而，Cur对ATO诱导的鸭下丘脑毒性的作用机制尚未完全阐明。在此，对鸭进行了为期28天的ATO和/或Cur处理；结果表明，暴露于ATO会导致鸭生长迟缓、羽毛凌乱和姿势异常。此外，ATO导致鸭下丘脑神经元空泡变性和崩解。同时，ATO诱导血脑屏障损伤，下调ZO-1、闭合蛋白的表达，并介导NF-κB激活，导致炎症因子（TLR-4、NF-κB、TNF-α、IL-2和IL-6）增加。此外，ATO增加了焦亡相关因子（半胱天冬酶-1、IL-18、IL-1）的产生，通过NLRP3介导的炎性小体激活加剧了炎症损伤。另一方面，Cur对炎症和焦亡具有优异的抑制作用。总之，我们的研究表明，ATO通过调节鸭下丘脑的NF-κB/NLRP3信号通路引发炎症和焦亡，而Cur可以减轻ATO引起的炎症和焦亡。因此，作为一种植物提取物，Cur具有预防和治疗ATO诱导的下丘脑毒性的潜力。
