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. 2023 Oct 1;264:115475. doi: 10.1016/j.ecoenv.2023.115475. Epub 2023 Sep 13.
To date, it is unclear whether deltamethrin (DLM) intake causes damage to colon tissue. Hence, in this study, we aimed to clarify the effect of long-term exposure to low-dose DLM on colon tissues, and its potential mechanisms.
Mice were treated with DLM (0.2 mg/kg/day) or DLM combined with N-acetyl-l-cysteine (NAC) (50 mg/kg/day) for 8 weeks. Human colon cancer cells (HCT-116) were treated with DLM (0, 25, 50, or 100 µM), NAC (2 mM), or overexpression plasmids targeting peroxiredoxin 1 (PRDX1) for 48 h. DLM was detected using a DLM rapid detection card. Colon injury was evaluated using haematoxylin and eosin staining and transmission electron microscopy. Apoptosis was determined using immunofluorescence staining (IF), western blotting (WB) and flow cytometry (FC) assays. MitoTracker, JC-1, and glutathione (GSH) detection were used to detect mitochondrial oxidative stress. Intestinal flora were identified by 16 S rDNA sequencing.
DLM accumulation was detected in the colon tissue and faeces of mice following long-term intragastric administration. Interestingly, our results showed that, even at a low dose, long-term intake of DLM resulted in severe weight loss and decreased the disease activity index scores and colon length. The results of IF, WB, and FC showed that DLM induced apoptosis in the colon tissue and cells. MitoTracker, JC-1, and GSH assays showed that DLM increased mitochondrial stress in colonic epithelial cells. Mechanistic studies have shown that increased mitochondrial stress and apoptosis are mediated by PRDX1 inhibition. Further experiments showed that PRDX1 overexpression significantly reduced DLM-induced oxidative stress injury and apoptosis. In addition, we observed that chronic exposure to DLM altered the composition of the intestinal flora in mice, including an increase in Odoribacter and Bacteroides and a decrease in Lactobacillus. The gut microbial richness decreased after DLM exposure in mice. Supplementation with NAC both in vivo and in vitro alleviated DLM-induced oxidative stress injury, colonic epithelial cell apoptosis, and gut microbial dysbiosis.
Chronic exposure to DLM, even at small doses, can cause damage to the colon tissue, which cannot be ignored. The production and use of pesticides such as DLM should be strictly regulated during agricultural production.
到目前为止，尚不清楚氯菊酯（DLM）摄入是否会对结肠组织造成损害。因此，本研究旨在阐明长期低剂量 DLM 暴露对结肠组织的影响及其潜在机制。
将小鼠用 DLM（0.2mg/kg/天）或 DLM 联合 N-乙酰-L-半胱氨酸（NAC）（50mg/kg/天）处理 8 周。用 DLM（0、25、50 或 100μM）、NAC（2mM）或过氧化物还原酶 1（PRDX1）过表达质粒处理人结肠癌细胞（HCT-116）48h。用 DLM 快速检测卡检测 DLM。用苏木精和伊红染色和透射电子显微镜评估结肠损伤。用免疫荧光染色（IF）、蛋白质印迹（WB）和流式细胞术（FC）检测细胞凋亡。用 MitoTracker、JC-1 和谷胱甘肽（GSH）检测来检测线粒体氧化应激。通过 16S rDNA 测序鉴定肠道菌群。
长期灌胃后，小鼠结肠组织和粪便中检测到 DLM 蓄积。有趣的是，我们的结果表明，即使在低剂量下，长期摄入 DLM 也会导致严重的体重减轻，并降低疾病活动指数评分和结肠长度。IF、WB 和 FC 的结果表明，DLM 诱导了结肠组织和细胞的凋亡。MitoTracker、JC-1 和 GSH 检测表明 DLM 增加了结肠上皮细胞的线粒体应激。机制研究表明，线粒体应激和细胞凋亡增加是由 PRDX1 抑制介导的。进一步的实验表明，PRDX1 过表达显著减轻了 DLM 诱导的氧化应激损伤和细胞凋亡。此外，我们观察到慢性暴露于 DLM 改变了小鼠的肠道菌群组成，包括 Odoribacter 和 Bacteroides 的增加以及 Lactobacillus 的减少。暴露于 DLM 后，小鼠肠道微生物丰富度降低。体内和体外补充 NAC 均可减轻 DLM 诱导的氧化应激损伤、结肠上皮细胞凋亡和肠道微生物失调。
即使在小剂量下，慢性暴露于 DLM 也会对结肠组织造成损害，这一点不容忽视。在农业生产中，应该严格监管 DLM 等农药的生产和使用。
