Chlorpyrifos induces cytotoxicity via oxidative stress and mitochondrial dysfunction in HepG2 cells.

Autor: Montanarí C; Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy and Food Sciences, Universitat de València, Av. Vicent Andrés Estellés s/n, Burjassot, 46100, València, Spain., Franco-Campos F; Research Group in Alternative Methods for Determining Toxic Effects and Risk Assessment of Contaminants and Mixtures (RiskTox), Spain; Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy and Food Sciences, Universitat de València, Av. Vicent Andrés Estellés s/n, Burjassot, 46100, València, Spain., Taroncher M; Research Group in Alternative Methods for Determining Toxic Effects and Risk Assessment of Contaminants and Mixtures (RiskTox), Spain; Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy and Food Sciences, Universitat de València, Av. Vicent Andrés Estellés s/n, Burjassot, 46100, València, Spain., Rodríguez-Carrasco Y; Research Group in Alternative Methods for Determining Toxic Effects and Risk Assessment of Contaminants and Mixtures (RiskTox), Spain; Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy and Food Sciences, Universitat de València, Av. Vicent Andrés Estellés s/n, Burjassot, 46100, València, Spain., Zingales V; Research Group in Alternative Methods for Determining Toxic Effects and Risk Assessment of Contaminants and Mixtures (RiskTox), Spain; Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy and Food Sciences, Universitat de València, Av. Vicent Andrés Estellés s/n, Burjassot, 46100, València, Spain. Electronic address: vezin@uv.es., Ruiz MJ; Research Group in Alternative Methods for Determining Toxic Effects and Risk Assessment of Contaminants and Mixtures (RiskTox), Spain; Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy and Food Sciences, Universitat de València, Av. Vicent Andrés Estellés s/n, Burjassot, 46100, València, Spain.
Jazyk: angličtina
Zdroj: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2024 Oct; Vol. 192, pp. 114933. Date of Electronic Publication: 2024 Aug 13.
DOI: 10.1016/j.fct.2024.114933
Abstrakt: Chlorpyrifos (CPF), a widely used broad-spectrum organophosphate pesticide, has been associated with various adverse health effects in animals and humans. While its primary mechanism of action involves the irreversible inhibition of acetylcholinesterase, secondary mechanisms have also been suggested. The aim of the present study was to explore the secondary mechanisms of action involved in CPF-induced acute cytotoxicity using human hepatocarcinoma HepG2 cells. In particular, we investigated oxidative stress and mitochondrial function by assessing reactive oxygen species (ROS) generation, lipid peroxidation (LPO) and mitochondrial membrane potential (ΔΨ m ) alteration. Results showed that 24-h exposure to CPF (78.125-2500 μM) decreased cell viability in a concentration-dependent manner (IC 50  = 280.87 ± 26.63 μM). Sub-toxic CPF concentrations (17.5, 35 and 70 μM) induced increases in ROS generation (by 83%), mitochondrial superoxide (by 7.1%), LPO (by 11%), and decreased ΔΨ m (by 20%). CPF also upregulated Nrf2 protein expression, indicating the role of the latter in modulating the cellular response to oxidative insults. Overall, our findings suggest that CPF caused hepatotoxicity through oxidative stress and mitochondrial dysfunction. Given the re-emerging use of CPF, this study emphasizes the need for comprehensive analysis to elucidate its toxicity on non-target organs and associated mechanisms.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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