Abstract：
Bisphenol A (BPA) is an industrial pollutant that can cause immune impairment. Selenium acts as an antioxidant, as selenium deficiency often accompanies oxidative stress, resulting in organ damage. This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell (MDCC-MSB-1) via oxidative stress-induced endoplasmic reticulum (ER) stress. We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days. The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities (T-AOC, CAT, and GSH-Px), accumulation of peroxides (H2O2 and MDA), significant upregulation of ER stress-related markers (GRP78, IER 1, PERK, EIF-2α, ATF4, and CHOP), a significant increase in iron ion levels, significant upregulation of pyroptosis-related gene (NLRP3, ASC, Caspase1, GSDMD, IL-18 and IL-1β), significantly increase ferroptosis-related genes (TFRC, COX2) and downregulate GPX4, HO-1, FTH, NADPH. In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results, demonstrating that the addition of antioxidant (NAC), ER stress inhibitor (TUDCA) and pyroptosis inhibitor (Vx765) alleviated oxidative stress, endoplasmic reticulum stress, pyroptosis, and ferroptosis. Overall, this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.
摘要：
双酚A(BPA)是一种可引起免疫损伤的工业污染物。硒作为抗氧化剂，硒缺乏通常伴随着氧化应激，导致器官损伤。这项研究首次证明了BPA和/或硒缺乏通过氧化应激诱导的内质网（ER）应激在鸡和鸡淋巴瘤细胞（MDCC-MSB-1）中诱导焦亡和铁凋亡介导的胸腺损伤。我们建立了BPA和/或硒缺乏暴露的肉鸡模型，并在42天后收集胸腺样本作为研究对象。结果表明，BPA或硒缺乏导致抗氧化酶活性降低（T-AOC，CAT,和GSH-Px），过氧化物（H2O2和MDA）的积累，内质网应激相关标志物(GRP78，IER1，PERK，EIF-2α,ATF4和CHOP），铁离子水平显著增加，焦亡相关基因显著上调(NLRP3，ASC，Caspase1,GSDMD,IL-18和IL-1β），显著增加铁凋亡相关基因(TFRC，COX2)并下调GPX4、HO-1、FTH、NADPH.在MDCC-MSB-1细胞中进行的体外实验证实了结果，证明添加抗氧化剂(NAC)，内质网应激抑制剂（TUDCA）和焦亡抑制剂（Vx765）缓解氧化应激，内质网应激,焦亡,和铁中毒。总的来说,本研究得出结论，氧化应激和内质网应激的联合作用介导了BPA暴露和硒缺乏引起的鸡胸腺的焦亡和铁凋亡。
