{"title":"接触溴氰菊酯可通过上调内质网应激介导的 TXNDC5 水平引起小鼠肾脏炎症和肾脏纤维化","authors":"","doi":"10.1016/j.pestbp.2024.106180","DOIUrl":null,"url":null,"abstract":"<div><div>Deltamethrin (DLM) is a type II pyrethroid insecticide that is extensively applied to agriculture, veterinary medicine and livestock pest control. Excessive accumulation of DLM in the body can lead to nephrotoxicity, but the precise toxic mechanism remains obscure. Therefore, we established in vivo models of DLM-exposed mice for 30 days and in vitro models of DLM-exposed renal tubular epithelial cells of mice. The results revealed adverse effects on renal function in mice exposed to excessive DLM, manifested as endoplasmic reticulum (ER) swelling, local inflammatory infiltration in renal tissue and increased collagen fibers, suggesting renal inflammation and fibrosis, etc. Subsequently, in vivo experiments, we found that DLM exposure increased expression levels of endoplasmic reticulum stress (ERS)-related factors, significantly upregulated the expression of TXNDC5, and enhanced the colocalization of GRP78 with TXNDC5. Notably, DLM exposure also strengthened the co-localization of TXNDC5 with NF-κB p65 and TGF-β1, upregulated the expression levels of TLR4/MYD88/NF-κB and TGF-β/SMAD2/3 pathways, alongside inflammation and fibrosis-related factors, these changes exhibited a dose-dependent effect. Meanwhile, in vitro experiments, the results of ERS, inflammation, and fibrosis-related factor expression levels were consistent with those observed in vivo. In conclusion, our results demonstrated that TXNDC5 might played a certain role in DLM-induced nephrotoxicity. Specifically, DLM exposure could trigger ERS, increase TXNDC5 expression, and promote TLR4/MYD88/NF-κB and TGF-β/Smad2/3 pathways, leading to renal inflammation and fibrosis in mice. These discoveries not only deepen our understanding of DLM toxicity but also provide valuable avenues for exploring mitigation strategies and therapeutic interventions.</div></div>","PeriodicalId":19828,"journal":{"name":"Pesticide Biochemistry and Physiology","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Deltamethrin exposure caused renal inflammation and renal fibrosis via upregulating endoplasmic reticulum stress-mediated TXNDC5 level in mice\",\"authors\":\"\",\"doi\":\"10.1016/j.pestbp.2024.106180\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Deltamethrin (DLM) is a type II pyrethroid insecticide that is extensively applied to agriculture, veterinary medicine and livestock pest control. Excessive accumulation of DLM in the body can lead to nephrotoxicity, but the precise toxic mechanism remains obscure. Therefore, we established in vivo models of DLM-exposed mice for 30 days and in vitro models of DLM-exposed renal tubular epithelial cells of mice. The results revealed adverse effects on renal function in mice exposed to excessive DLM, manifested as endoplasmic reticulum (ER) swelling, local inflammatory infiltration in renal tissue and increased collagen fibers, suggesting renal inflammation and fibrosis, etc. Subsequently, in vivo experiments, we found that DLM exposure increased expression levels of endoplasmic reticulum stress (ERS)-related factors, significantly upregulated the expression of TXNDC5, and enhanced the colocalization of GRP78 with TXNDC5. Notably, DLM exposure also strengthened the co-localization of TXNDC5 with NF-κB p65 and TGF-β1, upregulated the expression levels of TLR4/MYD88/NF-κB and TGF-β/SMAD2/3 pathways, alongside inflammation and fibrosis-related factors, these changes exhibited a dose-dependent effect. Meanwhile, in vitro experiments, the results of ERS, inflammation, and fibrosis-related factor expression levels were consistent with those observed in vivo. In conclusion, our results demonstrated that TXNDC5 might played a certain role in DLM-induced nephrotoxicity. Specifically, DLM exposure could trigger ERS, increase TXNDC5 expression, and promote TLR4/MYD88/NF-κB and TGF-β/Smad2/3 pathways, leading to renal inflammation and fibrosis in mice. These discoveries not only deepen our understanding of DLM toxicity but also provide valuable avenues for exploring mitigation strategies and therapeutic interventions.</div></div>\",\"PeriodicalId\":19828,\"journal\":{\"name\":\"Pesticide Biochemistry and Physiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-10-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pesticide Biochemistry and Physiology\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0048357524004139\",\"RegionNum\":1,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pesticide Biochemistry and Physiology","FirstCategoryId":"97","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0048357524004139","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Deltamethrin exposure caused renal inflammation and renal fibrosis via upregulating endoplasmic reticulum stress-mediated TXNDC5 level in mice
Deltamethrin (DLM) is a type II pyrethroid insecticide that is extensively applied to agriculture, veterinary medicine and livestock pest control. Excessive accumulation of DLM in the body can lead to nephrotoxicity, but the precise toxic mechanism remains obscure. Therefore, we established in vivo models of DLM-exposed mice for 30 days and in vitro models of DLM-exposed renal tubular epithelial cells of mice. The results revealed adverse effects on renal function in mice exposed to excessive DLM, manifested as endoplasmic reticulum (ER) swelling, local inflammatory infiltration in renal tissue and increased collagen fibers, suggesting renal inflammation and fibrosis, etc. Subsequently, in vivo experiments, we found that DLM exposure increased expression levels of endoplasmic reticulum stress (ERS)-related factors, significantly upregulated the expression of TXNDC5, and enhanced the colocalization of GRP78 with TXNDC5. Notably, DLM exposure also strengthened the co-localization of TXNDC5 with NF-κB p65 and TGF-β1, upregulated the expression levels of TLR4/MYD88/NF-κB and TGF-β/SMAD2/3 pathways, alongside inflammation and fibrosis-related factors, these changes exhibited a dose-dependent effect. Meanwhile, in vitro experiments, the results of ERS, inflammation, and fibrosis-related factor expression levels were consistent with those observed in vivo. In conclusion, our results demonstrated that TXNDC5 might played a certain role in DLM-induced nephrotoxicity. Specifically, DLM exposure could trigger ERS, increase TXNDC5 expression, and promote TLR4/MYD88/NF-κB and TGF-β/Smad2/3 pathways, leading to renal inflammation and fibrosis in mice. These discoveries not only deepen our understanding of DLM toxicity but also provide valuable avenues for exploring mitigation strategies and therapeutic interventions.
期刊介绍:
Pesticide Biochemistry and Physiology publishes original scientific articles pertaining to the mode of action of plant protection agents such as insecticides, fungicides, herbicides, and similar compounds, including nonlethal pest control agents, biosynthesis of pheromones, hormones, and plant resistance agents. Manuscripts may include a biochemical, physiological, or molecular study for an understanding of comparative toxicology or selective toxicity of both target and nontarget organisms. Particular interest will be given to studies on the molecular biology of pest control, toxicology, and pesticide resistance.
Research Areas Emphasized Include the Biochemistry and Physiology of:
• Comparative toxicity
• Mode of action
• Pathophysiology
• Plant growth regulators
• Resistance
• Other effects of pesticides on both parasites and hosts.