Aline Mocellin Conte, Fernanda Mocellin Conte, Larissa V Cestonaro, Maria Fernanda Nunes Ribeiro, Rodrigo F da Silva, Renata De Faveri, Larissa Benvenutti, Solange C Garcia, José Roberto Santin, Rodrigo Ligabue-Braun, Bruno Dutra Arbo, Marcelo Dutra Arbo
{"title":"Flumetralin based plant growth regulator used in tobacco cultivation induces immune and cytotoxicity in vitro.","authors":"Aline Mocellin Conte, Fernanda Mocellin Conte, Larissa V Cestonaro, Maria Fernanda Nunes Ribeiro, Rodrigo F da Silva, Renata De Faveri, Larissa Benvenutti, Solange C Garcia, José Roberto Santin, Rodrigo Ligabue-Braun, Bruno Dutra Arbo, Marcelo Dutra Arbo","doi":"10.1093/toxres/tfaf118","DOIUrl":null,"url":null,"abstract":"<p><p>Tobacco production lasts about 10 months and various pesticides are used, including growth inhibitors, which flumetralin is the most used. This is an herbicide that acts as a synthetic and plant growth regulator. Therefore, this work aimed to evaluate the toxicity of the growth regulator flumetralin in RAW 264.7 and 3T3 cell lines. Cytotoxicity was assessed by MTT reduction and neutral red uptake assays after 24 h of incubation with flumetralin. Mitochondrial integrity, production of reactive species and cytokine profile were evaluated in both cell lines. Furthermore, NO production was evaluated in RAW 264.7 cells, while comet assay was evaluated in 3T3 cells. An increase in reactive species production was observed in both cell lines. In RAW 264.7 cells were observed an increase in mitochondrial membrane potential, while 3T3 cells presented a mitochondrial depolarization. At all tested concentrations, flumetralin increased TNF-α levels and decreased IL-10 levels in RAW 264.7, and increased TNF and IL-1ß in 3T3 cells. In addition, at all tested concentrations, flumetralin induced DNA damage in 3T3 cells. It was possible to observe the cytotoxic effect of flumetralin on the tested cell lines, as well as a possible generation of an inflammatory response and immune deregulation.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf118"},"PeriodicalIF":2.1000,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371405/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/toxres/tfaf118","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Tobacco production lasts about 10 months and various pesticides are used, including growth inhibitors, which flumetralin is the most used. This is an herbicide that acts as a synthetic and plant growth regulator. Therefore, this work aimed to evaluate the toxicity of the growth regulator flumetralin in RAW 264.7 and 3T3 cell lines. Cytotoxicity was assessed by MTT reduction and neutral red uptake assays after 24 h of incubation with flumetralin. Mitochondrial integrity, production of reactive species and cytokine profile were evaluated in both cell lines. Furthermore, NO production was evaluated in RAW 264.7 cells, while comet assay was evaluated in 3T3 cells. An increase in reactive species production was observed in both cell lines. In RAW 264.7 cells were observed an increase in mitochondrial membrane potential, while 3T3 cells presented a mitochondrial depolarization. At all tested concentrations, flumetralin increased TNF-α levels and decreased IL-10 levels in RAW 264.7, and increased TNF and IL-1ß in 3T3 cells. In addition, at all tested concentrations, flumetralin induced DNA damage in 3T3 cells. It was possible to observe the cytotoxic effect of flumetralin on the tested cell lines, as well as a possible generation of an inflammatory response and immune deregulation.