Chronic oral exposure to cadmium causes liver inflammation by NLRP3 inflammasome activation in pubertal mice
Chronic oral exposure to cadmium causes liver inflammation by NLRP3 inflammasome activation in pubertal mice
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DOI：
10.1016/j.fct.2020.111944
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发表时间：
2021-02-01
影响因子：
4.3
通讯作者：
Bai, Weibin
中科院分区：
文献类型：
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作者：
Li, Xusheng;Li, Haiwei;Bai, Weibin
镉（Cd）是一种潜在的有毒微量元素，经常存在于食物、水和空气中，其持续的生物积累和诱导氧化应激和炎症威胁肝功能。然而，Cd在青春期的肝毒性尚不清楚。在本研究中，青春期小鼠给予氯化镉5.0 mg/kg的剂量。分别于10、20、30天不同治疗时间观察大鼠肝脏损伤情况。Cd暴露后，第20天出现明显的炎性肝细胞浸润，凋亡细胞增多，第30天循环中丙氨酸转氨酶和天冬氨酸转氨酶增加。此外，肝脏中tnf - α和MCP-1升高，促炎因子（IL-1 α、IL-1 β和IL-18）和抗炎因子（tgf - β、IL-10和IL-13） mRNA表达均显著上调。此外，活化的Ml和M2巨噬细胞负责这些细胞因子的释放。最重要的是，这些数据证实了nod样受体pyrin结构域3 （NLRP3）炎症小体在青春期cd诱导的肝脏炎症中的关键作用。总之，我们的研究结果表明，低剂量的Cd口服暴露可通过激活NLRP3炎性体引起肝脏炎症，并在青春期引起严重的肝损伤。
Cadmium (Cd) is a potentially toxic trace element frequently existed in foods, water, and air, threatening liver function from its continuous bioaccumulation and induction of oxidative stress and inflammation. However, the hepatotoxicity of Cd during puberty remains unclear. In this study, pubertal mice were given cadmium chloride at a dose of 5.0 mg/kg.bw by gavage, and the liver damage was investigated at different treatment points of 10, 20, and 30 days. After Cd exposure, there is an obvious inflammatory hepatocyte infiltration accompanied by more apoptotic cells at 20 days and an increase in alanine aminotransferases and aspartate aminotransferases in circulation at 30 days. Additionally, the soaring TNF-alpha and MCP-1 were found in liver, and the mRNA expression of pro-inflammatory cytokines (IL-1 alpha, IL-1 beta, and IL-18) and anti-inflammatory cytokines (TGF-beta, IL-10, and IL-13) were both significantly upregulated. Moreover, the activated Ml and M2 macrophages were confirmed in charge of these cytokines release. Most importantly, the data validated a pivotal role of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in Cd-induced inflammation in liver at puberty. Collectively, our results suggested that low-dose Cd oral exposure can cause liver inflammation via activation of NLRP3 inflammasome and give rise to severe liver injury at puberty.