Department of Core Medical Laboratory, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan 511518, PR China.
Department of Pathophysiology, College of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, Sichuan Province, PR China.
Ecotoxicol Environ Saf. 2021 Oct 1;222:112529. doi: 10.1016/j.ecoenv.2021.112529. Epub 2021 Jul 19.
Mercury is a naturally occurring element and highly toxic to humans even at a low dosage. Curcumin is a polyphenol found in turmeric (Curcuma longa), widely used as a treatment strategy to improve antioxidant and anti-inflammatory properties. The purpose of this study was to investigate the potential protective mechanisms of curcumin in spleen damage induced by HgCl. The mice were given curcumin by intragastric administration 2 h before HgCl injection for 24 h. At first, splenic transcriptome analysis showed that 3334 genes (2134 up and 1200 down) were differently expressed in HgCl-induced spleen damage model. Notably, KEGG enrichment showed phosphatidylinositol 3-kinase (PI3K)-AKT might be a key signaling pathways in HgCl-induced spleen damage. Furthermore, our data demonstrated that HgCl could induce autophagic cell death, evidenced by increases the protein expression of PI3K, AKT, LC3-II and p62 and the number of apoptotic cells. Furthermore, we found that curcumin significantly combated autophagic cell death, sodium overload and calcium leak induced by HgCl. Simultaneously, further studies demonstrated that curcumin significantly activated nuclear factor (erythroid-derived-2)-like 2 (Nrf2) signaling pathway, and subsequent enhancing antioxidant defenses. Taken together, our data indicated that inorganic mercury could result in autophagic cell death, which may be related to the regulation of PI3K-AKT signaling cascades. Furthermore, Nrf2-mediated antioxidant defenses may be the target of curcumin to confers an adaptive survival response to resist spleen damage induced by HgCl. The present study perfects the mechanism theory of HgCl-induced spleen damage and provides a way for pharmacological intervention to prevent spleen injury.
汞是一种天然存在的元素，即使剂量很低，对人类也具有高度毒性。姜黄素是姜黄（Curcuma longa）中发现的一种多酚，广泛用作改善抗氧化和抗炎特性的治疗策略。本研究的目的是研究姜黄素在 HgCl 诱导的脾损伤中的潜在保护机制。将姜黄素通过胃内给药给予小鼠，在 HgCl 注射前 2 小时给药 24 小时。首先，脾转录组分析表明，HgCl 诱导的脾损伤模型中 3334 个基因（2134 个上调和 1200 个下调）表达不同。值得注意的是，KEGG 富集表明磷脂酰肌醇 3-激酶（PI3K）-AKT 可能是 HgCl 诱导的脾损伤的关键信号通路。此外，我们的数据表明，HgCl 可以诱导自噬细胞死亡，证据是增加 PI3K、AKT、LC3-II 和 p62 的蛋白表达以及凋亡细胞的数量。此外，我们发现姜黄素可显著对抗 HgCl 诱导的自噬细胞死亡、钠过载和钙漏。同时，进一步的研究表明，姜黄素可显著激活核因子（红系衍生 2）样 2（Nrf2）信号通路，随后增强抗氧化防御。总之，我们的数据表明，无机汞可能导致自噬细胞死亡，这可能与 PI3K-AKT 信号级联的调节有关。此外，Nrf2 介导的抗氧化防御可能是姜黄素赋予适应性生存反应以抵抗 HgCl 诱导的脾损伤的靶点。本研究完善了 HgCl 诱导的脾损伤的机制理论，并为药理学干预提供了一种预防脾损伤的方法。
