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This study demonstrated that cytotoxicity, expression of transient receptor potential cation channel subfamily A member 1 (TRPA1) mRNA, and intracellular calcium influx were increased in A549 cells exposed to amide herbicides (AHs), in which the order of cytotoxicity was metolachlor &gt; acetochlor &gt; propisochlor &gt; alachlor &gt; butachlor &gt; propanil &gt; pretilachlor, based on IC50 values of 430, 524, 564, 565, 619, 831, and 2333 \u03bcM, respectively. Inhibition\/knockout of TRPA1 efficiently protected against cytotoxicity, decreased TRPA1 mRNA expression, and reduced calcium influx. The results suggested that the TRPA1 channel could be a key common target for AHs poisoning. The order of TRPA1 affinity for AHs was propanil &gt; pretilachlor &gt; metolachlor &gt; (propiso\/ala\/aceto\/butachlor), based on KD values of 16.2, 309, and 364 \u03bcM, respectively. The common molecular mechanisms of TRPA1-AHs interactions were clarified, including toxicity-effector groups (benzene ring, nitrogen\/oxygen-containing functional groups, halogen) and residues involved in interactions (Lys787, Leu982). This work provides valuable information for the development of TRPA1 as a promising therapeutic target for broad-spectrum antitoxins.<\/jats:p>","DOI":"10.3390\/ijerph19137985","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T20:47:56Z","timestamp":1656535676000},"page":"7985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Potential Common Mechanisms of Cytotoxicity Induced by Amide Herbicides via TRPA1 Channel Activation"],"prefix":"10.3390","volume":"19","author":[{"given":"Xiaoning","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Process Equipment and Environmental Engineering, School of Mechanical Engineering and Automation, Northeastern University, Shenyang 110819, China"},{"name":"State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangyang","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengying","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weijie","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Sui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minmin","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenyu","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Process Equipment and Environmental Engineering, School of Mechanical Engineering and Automation, Northeastern University, Shenyang 110819, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10399","DOI":"10.1021\/acs.est.0c02070","article-title":"Biodegradation and Abiotic Degradation of Trifluralin: A Commonly Used Herbicide with a Poorly Understood Environmental Fate","volume":"54","author":"Coleman","year":"2020","journal-title":"Environ. 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