College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China; Animal Disease Control and Prevention of Heilongjiang Province, No. 243 Haping Road, Xiangfang District, Harbin, 150069, China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, PR China.
Ecotoxicol Environ Saf. 2020 Nov;204:111049. doi: 10.1016/j.ecoenv.2020.111049. Epub 2020 Aug 3.
Recent studies identified a novel programmed and regulated cell death that was characterized by a necrotic cell death morphology, termed necroptosis. Lead (Pb) is known as a persistent inorganic environmental pollutant that affects the health of humans and animals worldwide. However, there are no detailed reports of Pb-induced necroptosis of immune tissue. Selenium (Se) is a trace element that antagonizes the toxicity of heavy metals. Here, chickens were randomly divided into four groups, treated with Pb ((CHOO)Pb, 150 mg/kg) and/or Se (NaSeO, 2 mg/kg), aim to study the effect and mechanism of necroptosis in Pb-induced spleen injury and the antagonistic effects of Se on Pb toxicity. Our results showed that Pb exposure evidently increased the accumulation of Pb in spleen and caused necroptosis by upregulating the expression of RIP1, RIP3 and MLKL, and decreasing Caspase8 expression. Meanwhile, Pb treatment inhibited the activities of SOD, GPX, and CAT, caused the accumulation of NO and MDA, and induced oxidative stress, which promoted the expression of MAPK/NF-κB pathway genes (ERK, JNK, P38, NF-κB and TNF-α) and activated HSPs (HSP27, HSP40, HSP60, HSP70 and HSP90). However, the increased content of Pb in spleen and Pb-caused necroptosis were inhibited by Se cotreatment. Overall, we conclude that Se can prevent Pb-induced necroptosis by restoring antioxidant functions and blocking the MAPK/NF-κB pathway and HSPs activation in chicken spleen.
最近的研究确定了一种新型的程序性和调节性细胞死亡，其特征是坏死性细胞死亡形态，称为坏死性细胞死亡。铅 (Pb) 是一种已知的持久性无机环境污染物，影响全球人类和动物的健康。然而，目前尚无关于 Pb 诱导免疫组织坏死性细胞死亡的详细报道。硒 (Se) 是一种微量元素，可拮抗重金属的毒性。在这里，鸡被随机分为四组，用 Pb ((CHOO)Pb，150mg/kg) 和/或 Se (NaSeO，2mg/kg) 处理，旨在研究 Pb 诱导的脾脏损伤中坏死性细胞死亡的作用和机制，以及 Se 对 Pb 毒性的拮抗作用。我们的结果表明，Pb 暴露明显增加了脾脏中 Pb 的积累，并通过上调 RIP1、RIP3 和 MLKL 的表达，降低 Caspase8 的表达，导致坏死性细胞死亡。同时，Pb 处理抑制了 SOD、GPX 和 CAT 的活性，导致 NO 和 MDA 的积累，并诱导氧化应激，这促进了 MAPK/NF-κB 途径基因（ERK、JNK、P38、NF-κB 和 TNF-α）和热休克蛋白（HSPs）（HSP27、HSP40、HSP60、HSP70 和 HSP90）的表达。然而，Se 共处理抑制了 Pb 增加的脾脏含量和 Pb 引起的坏死性细胞死亡。总的来说，我们得出结论，Se 可以通过恢复抗氧化功能和阻断 MAPK/NF-κB 途径和 HSPs 激活来防止 Pb 诱导的鸡脾脏坏死性细胞死亡。
