Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Ecotoxicol Environ Saf. 2024 Apr 1;274:116214. doi: 10.1016/j.ecoenv.2024.116214. Epub 2024 Mar 14.
Deltamethrin (DLM) is a commonly used insecticide, which is harmful to many organs. Here, we explored the effects of chronic low-dose DLM residues on colon tissue and its potential mechanism.
The mice were given long-term low-dose DLM by intragastric administration, and the body weights and disease activity index (DAI) scores of the mice were regularly recorded. The colon tissues were then collected for hematoxylin-eosin, immunofluorescence and immunohistochemistry staining. Besides, the RNA sequencing was performed to explore the potential mechanism.
Our results showed that long-term exposure to low-dose DLM could cause inflammation in mice colon tissue, manifested as weight loss, increased DAI score, increased apoptosis of colonic epithelial cells, and increased infiltration of inflammatory cells. However, we observed that after long-term exposure to DLM and withdrawal for a period of time, although apoptosis was restored, the recovery of colon inflammation was not ideal. Subsequently, we performed RNA sequencing and found that long-term DLM exposure could lead to the senescence of some cells in mice colon tissue. The results of staining of cellular senescence markers in colon tissue showed that the level of cellular senescence in the DLM group was significantly increased, and the p53 signalling related to senescence was also significantly activated, indicating that cellular senescence played a key role in DLM-induced colitis. We further treated mice with quercetin (QUE) after long-term DLM exposure, and found that QUE could indeed alleviate DLM-induced colitis. In addition, we observed that long-term accumulation of DLM could aggravate DSS-induced colitis in mice, and QUE treatment could reverse this scenario.
Continuous intake of DLM caused chronic colitis in mice, and the inflammation persisted even after discontinuation of DLM intake. This was attributed to the induction of cellular senescence in colon tissue. Treatment with QUE alleviated DLM-induced colitis by reducing cellular senescence. Long-term DLM exposure also aggravated DSS-induced colitis, which could be mitigated by QUE treatment.
溴氰菊酯（DLM）是一种常用的杀虫剂，对许多器官都有危害。本研究旨在探讨慢性低剂量 DLM 残留对结肠组织的影响及其潜在机制。
通过灌胃给予小鼠长期低剂量 DLM，定期记录小鼠的体重和疾病活动指数（DAI）评分。收集结肠组织进行苏木精-伊红、免疫荧光和免疫组织化学染色。此外，还进行了 RNA 测序以探讨潜在机制。
长期接触低剂量 DLM 可导致小鼠结肠组织炎症，表现为体重减轻、DAI 评分升高、结肠上皮细胞凋亡增加和炎症细胞浸润增加。然而，我们观察到，长期暴露于 DLM 并停药一段时间后，尽管凋亡得到恢复，但结肠炎症的恢复并不理想。随后，我们进行了 RNA 测序，发现长期 DLM 暴露可导致小鼠结肠组织中某些细胞衰老。结肠组织中细胞衰老标志物染色的结果表明，DLM 组细胞衰老水平明显升高，与衰老相关的 p53 信号也明显激活，表明细胞衰老在 DLM 诱导的结肠炎中起关键作用。我们进一步在长期 DLM 暴露后用槲皮素（QUE）处理小鼠，发现 QUE 确实可以缓解 DLM 诱导的结肠炎。此外，我们观察到长期 DLM 蓄积可加重小鼠 DSS 诱导的结肠炎，而 QUE 治疗可逆转这种情况。
持续摄入 DLM 可导致小鼠慢性结肠炎，即使停止摄入 DLM，炎症仍持续存在。这归因于结肠组织中细胞衰老的诱导。QUE 通过减少细胞衰老缓解 DLM 诱导的结肠炎。长期 DLM 暴露还加重了 DSS 诱导的结肠炎，QUE 治疗可减轻这种情况。
