Tehran University of Medical Sciences Acta Medica Iranica 0044-6025 58 11 2021 01 01 552 561 Zeynab Shahmahmoodi Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Somayeh Jafarinejad Finetech in Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran. Mohammad Reza Hormozi-Nezhad Department of Chemistry, Sharif University of Technology, Tehran, Iran. Homanaz Ghafari Department of Pharmacology, School of Medicine, Tehran University of medical science, Tehran, Iran Mahmoud Ghazi khansari Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 2020 07 11 2020 07 12 Malathion is an organophosphorus insecticide widely used in agriculture, residential area, and public health programs with a known mechanism of toxicity of inhibition of acetylcholinesterase and induction of oxidative stress. Gold nanoparticles (AuNPs) represent stable and easily synthesized nanoparticles with extensive use in consumer products and medicine. Due to the antioxidant property of AuNPs, it is possible that AuNPs may prevent malathion-induced oxidative damage. In this study, the cytotoxicity of malathion and AuNPs (10 and 20 nm) were measured separately in Caco-2 cells. Then the protective effects of AuNPs were evaluated by measuring the oxidative stress (lipid peroxidation level and glutathione content) and acetylcholinesterase activity. The calculated IC50s values at 48 hr were 326.8±0.32, 43.09±0.65, and 41.46±0.24 µg/ml for malathion, AuNPs 10 and 20 nm, respectively. Then, the lowest concentration of AuNPs (1 µg/ml) and IC50 concentration of malathion (326.8 µg/ml) were selected to evaluate the effects of pretreatment of Caco-2 cells with AuNPs before exposure to malathion were evaluated. Interestingly, the results showed remarkably significant protective effects of AuNPs by attenuation the different parameters of oxidative stress and cytotoxicity induced by malathion in cells (P<0.001). It is the first report showing the protective effects of AuNPs against malathion-induced cytotoxicity in the Caco-2 cell line. https://acta.tums.ac.ir/index.php/acta/article/view/8619