Residue of thiram in food, suppresses immune system stress signals and disturbs sphingolipid metabolism in chickens
Residue of thiram in food, suppresses immune system stress signals and disturbs sphingolipid metabolism in chickens
复制标题
DOI：
10.1016/j.vetimm.2022.110415
复制
发表时间：
2022-03-25
影响因子：
1.8
通讯作者：
Zhang, Hui
中科院分区：
文献类型：
--
作者：
Liu, Yingwei;Yi, Jiangnan;Zhang, Hui
Thiram是一种众所周知的含硫有机化合物，因其具有很高的生物活性而被广泛应用于农业中，以控制不同的害虫。在某些情况下，由于农药和其他环境污染物长期存在于环境中，对公众健康和环境造成不良的毒性影响。为研究喜甜对肉仔鸡不同免疫器官的毒性作用机制，选取1日龄雏鸡100只，随机分为喜甜组（50 mg/kg）和未处理对照组。14日龄时采集实验鸟胸腺和脾脏组织。尸检水平胸腺充血、肿大、充血，脾脏未见明显病变。免疫毒性机制（凋亡和自噬）结果显示，处理小鼠脾脏中bax、caspase3、cytc、ATG5、beclin1和p62的表达显著升高。结果表明，m-TOR和bcl2的表达明显降低，可激活细胞凋亡和自噬。胸腺中bax、p53、m-TOR表达上调，ATG5、Beclin1表达下调，介导细胞凋亡，抑制自噬。不同代谢组学研究结果表明，暴露于thiram的雏鸡胸腺鞘脂代谢被破坏，导致SM、半乳糖神经酰胺和乳糖神经酰胺等与细胞膜成分相关的代谢物上调。我们的实验研究结果表明，thiram可以干扰胸腺鞘脂代谢和血管生成，抑制血管内皮细胞的增殖，从而引起鸡的潜在毒性作用。
Thiram, a well-known sulfur containing organic compound is frequently and extensively used in agriculture because of high biological activity to control different pests. In certain cases, due to long persistence in the environment pesticides and other environmental contaminants induce undesirable toxic impacts to public health and environment. To ascertain the potential mechanisms of toxicity of thiram on different immune organs of broilers, a total of 100 one-day-old chicks were obtained and randomly divided into two groups including thiram group (50 mg/kg) and untreated control group. Thymus and spleen tissues were collected at the age of 14 days from the experimental birds. At necropsy level, thymus was congested, enlarged and hyperemic while spleen had no obvious lesions. The results on mechanisms (apoptosis and autophagy) of immunotoxicity showed significantly increased expression of bax, caspase3, cytc, ATG5, beclin1 and p62 in spleen of treated mice. Results indicated significantly decreased expression of m-TOR and bcl2 to activate apoptosis and autophagy. The expressions of bax, p53 and m-TOR were up-regulated in the thymus while the expressions of ATG5 and Beclin1 were down-regulated to mediate cell apoptosis and inhibit autophagy. The results on different metabolome investigation showed that the sphingolipid metabolism in the thymus of chicks exposed to thiram was disrupted resulting in up-regulation of metabolites related to cell membrane components such as SM, galactosylceramide and lactosylceramide. The results of our experimental research suggest that thiram can interfere with the sphingolipid metabolism in thymus and angiogenesis, inhibit the proliferation of vascular endothelial cells to induce potential toxic effects in chicken.