Mecanismos de citotoxicidade do diuron em células uroteliais – possível papel de lesão mitocondrial
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Data
2022-03-30
Autores
Lima, Thania Rios Rossi
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Universidade Estadual Paulista (Unesp)
Resumo
Os efeitos tóxicos de substâncias químicas sobre o sistema urinário têm sido estudados ao longo dos últimos anos, sendo que o herbicida diuron e seus metabólitos mostraram potencial cancerígeno na bexiga urinária de ratos Wistar e citotoxicidade em células uroteliais derivadas de ratos e humanos. Assim, estudos que buscam elucidar os principais eventos envolvidos na toxicidade desses compostos são essenciais para compreender o possível mecanismo de ação sobre o urotélio. Este estudo teve como objetivo investigar os mecanismos de toxicidade urotelial exercida pelo diuron e metabólitos, abordando o possível papel da disfunção mitocondrial. Após exposição aos produtos químicos, as células uroteliais humanas 1T1 apresentaram alterações relacionadas à morte e proliferação, instabilidade do ciclo celular, estresse oxidativo, e dano mitocondrial. Além disso, por meio de investigação metabolômica em mitocôndrias uroteliais isoladas de ratos Wistar foram encontradas alterações em moléculas associadas à membrana e em moléculas envolvidas no metabolismo celular. Avaliados em conjunto, tais resultados indicam potencial ação nociva do diuron e seus metabólitos sobre a função mitocondrial, o que pode ser considerado o evento iniciador de um processo sequencial que desencadeia a citotoxicidade observada neste estudo e as alterações morfológicas observadas em estudos anteriores.
The toxic effects of chemical substances on the urinary system have been studied over the past years, being that the diuron herbicide and its metabolites showed carcinogenic potential in the urinary bladder of Wistar rats and cytotoxicity in rat and human-derived urothelial cells. Thus, studies that seek to elucidate the keyevents involved in the toxicity of these compounds are essential to understand the possible mechanism of action on the urothelium. This study aimed to investigate the underlying mechanisms linked to urothelial toxicity resulting from diuron and metabolites exposure, addressing the possible role of mitochondrial dysfunction. After exposure to the chemicals, human urothelial cells 1T1 showed alterations related to death and proliferation, cell cycle instability, oxidative stress, mitochondrial and damage. Additionally, through metabolomic investigation in urothelial mitochondria isolated from Wistar rats, alterations in membrane-associated molecules and in molecules involved in cellular metabolism were found. Altogether, these results indicate potential harmful action of diuron and its metabolites on mitochondrial function, which can be considered the initiator event of a sequential process that triggers the cytotoxicity observed in this study and the morphological changes observed in previous studies.
The toxic effects of chemical substances on the urinary system have been studied over the past years, being that the diuron herbicide and its metabolites showed carcinogenic potential in the urinary bladder of Wistar rats and cytotoxicity in rat and human-derived urothelial cells. Thus, studies that seek to elucidate the keyevents involved in the toxicity of these compounds are essential to understand the possible mechanism of action on the urothelium. This study aimed to investigate the underlying mechanisms linked to urothelial toxicity resulting from diuron and metabolites exposure, addressing the possible role of mitochondrial dysfunction. After exposure to the chemicals, human urothelial cells 1T1 showed alterations related to death and proliferation, cell cycle instability, oxidative stress, mitochondrial and damage. Additionally, through metabolomic investigation in urothelial mitochondria isolated from Wistar rats, alterations in membrane-associated molecules and in molecules involved in cellular metabolism were found. Altogether, these results indicate potential harmful action of diuron and its metabolites on mitochondrial function, which can be considered the initiator event of a sequential process that triggers the cytotoxicity observed in this study and the morphological changes observed in previous studies.
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Palavras-chave
Diuron, Disfunção mitocondrial, Cultura celular, Toxicidade urotelial, Herbicida