Elucidating the toxicity of methyl parathion, imazapic, isoxaflutole, and chlorantraniliprole on human hepatocarcinoma cells and bioinspired membranes

Author(s)

dos Santos, Daniela Mayra ; Rubira, Rafael J. G. ; Salzedas, Gabriela P. ; Kobal, Mirella B. ; Moreira, Lucas G. ; Toledo, Karina A. ; Aoki, Pedro H. B. ; Dewolf, Christine ; Camacho, Sabrina A.

• Document type: Journal article
• Source: JOURNAL OF HAZARDOUS MATERIALS; v. 490, p. 11-pg., 2025-02-27.

Abstract

Pesticides have boosted agricultural productivity but pose significant risks to environmental and human health. The intensification of agriculture has driven widespread pesticide use, with 66 % of global consumption allocated to sugarcane, soybean and corn. Sugarcane, a major monoculture in Brazil, India, and China, has driven a 700 % increase in pesticide use in Brazil over the past 40 years. Commonly used pesticides in Brazilian sugarcane farming include methyl parathion (PM), imazapic (IM), isoxaflutole (IS), and chlorantraniliprole (CL). Despite regulatory efforts by governmental agencies worldwide, the long-term toxicity of these substances on human health remains insufficiently studied. This study evaluates the cytotoxicity of PM, IM, IS, and CL at concentrations regulated by governmental agencies in human hepatocarcinoma (HepG2) cells. Given the liver's role in metabolizing xenobiotics, it is especially vulnerable to pesticide-toxicity. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide) and LDH (lactate dehydrogenase release) assays, alongside confocal microscopy, showed reduced cell viability and impaired membrane integrity, with progressive toxicity (from 24 to 96 h), primarily impacting mitochondrial activity. Surface pressure-area (pi-A) isotherms, compressibility (CS-1), and atomic force microscopy (AFM) revealed distinct pesticide incorporation mechanisms into Langmuir monolayers of HepG2 lipid extracts, used as membrane models. The findings underscore the hepatotoxicity of PM, IM, IS, and CL, even at concentrations regulated by governmental agencies, emphasizing their potential human health hazards. (AU)

• FAPESP's process: 20/05423-0 - Detection of pesticides (cocktails) used in sugarcane crops and their effect on biological systems
• Grantee: Rafael Jesus Gonçalves Rubira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/22214-6 - Towards a convergence of technologies: from sensing and biosensing to information visualization and machine learning for data analysis in clinical diagnosis
• Grantee: Osvaldo Novais de Oliveira Junior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 22/15310-4 - Evaluation of the cumulative cytotoxic effect of pesticides applied in sugarcane crops on cells derived from human lung carcinoma (A549)
• Grantee: Gabriela Peres Salzedas
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 20/15854-9 - Modulating photochemical reactions in Escherichia coli lipid monolayers with the binding mechanisms of eosin decyl ester and toluidine blue-O photosensitizers
• Grantee: Lucas Gontijo Moreira
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 21/14500-1 - Towards convergence of photodynamic (TFD) and photothermal (TFT) therapies on in vitro culture of melanoma-derived cells
• Grantee: Mirella Boaro Kobal
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 24/15686-0 - Multifunctional approach of gold nanostructures coated with silica: combining the diagnosis of circulating cancer cells with the tumor phototherapy
• Grantee: Sabrina Aléssio Camacho
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 23/17867-9 - Multifunctional approach of gold nanostructures coated with silica: combining the diagnosis of circulating cancer cells with the tumor phototherapy
• Grantee: Sabrina Aléssio Camacho
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 21/11344-9 - Cytotoxicity evaluation of pesticides employed in sugarcane crops in the in vitro culture of cells derived from human hepatocarcinoma (HepG2)
• Grantee: Daniela Mayra dos Santos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 22/02189-2 - Plasmonic nanostructures for synergistic photodynamic (PDT) and photothermal (PTT) therapy of cancer cells
• Grantee: Pedro Henrique Benites Aoki
• Support Opportunities: Research Grants - Initial Project
• FAPESP's process: 14/11408-3 - Multi-User Equipment approved in grant 2013/14262-7: confocal microscope
• Grantee: Osvaldo Novais de Oliveira Junior
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 22/15041-3 - Unveiling molecular interactions of pesticides in biomimetic membranes from human hepatocarcinoma (HepG2) cells
• Grantee: Daniela Mayra dos Santos
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation