Oxidative stress and DNA damage in agricultural workers after exposure to pesticides

Ledda, Caterina; Cannizzaro, Emanuele; Cinà, Diana; Filetti, Veronica; Vitale, Ermanno; Paravizzini, Gianluca; Naso, Concettina Di; Iavicoli, Ivo; Rapisarda, Venerando

doi:10.1186/s12995-020-00290-z

Cited by 49 publications

(26 citation statements)

References 46 publications

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“…Pesticides comprise a vast number of compounds, with different chemical structures, different organisms, and molecular targets as well as biological effects being used for crop and postharvest protection in the agricultural sector [ 1 , 2 ]. The term pesticide includes fungicides, herbicides, insecticides, molluscicides, nematicides, rodenticides, plant growth regulators, and other compounds which are classified according to the target pest [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Physicochemical Properties of Selected Pesticides as Predictive Factors for Oxidative Stress and Apoptosis-Dependent Cell Death in Caco-2 and HepG2 Cells

Silva

Martins-Gomes

Ferreira

et al. 2022

IJMS

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In this work, three pesticides of different physicochemical properties: glyphosate (GLY, herbicide), imidacloprid (IMD, insecticide), and imazalil (IMZ, fungicide), were selected to assess their cytotoxicity against Caco-2 and HepG2 cells. Cell viability was assessed by the Alamar Blue assay, after 24 and 48 h exposure to different concentrations, and IC50 values were calculated. The mechanisms underlying toxicity, namely cellular reactive oxygen species (ROS), glutathione (GSH) content, lipid peroxidation, loss of mitochondrial membrane potential (MMP), and apoptosis/necrosis induction were assessed by flow cytometry. Cytotoxic profiles were further correlated with the molecular physicochemical parameters of pesticides, namely: water solubility, partition coefficient in an n-octanol/water (Log Pow) system, topological polar surface area (TPSA), the number of hydrogen-bonds (donor/acceptor), and rotatable bonds. In vitro outputs resulted in the following toxicity level: IMZ (Caco-2: IC50 = 253.5 ± 3.37 mM, and HepG2: IC50 = 94 ± 12 mM) > IMD (Caco-2: IC50 > 1 mM and HepG2: IC50 = 624 ± 24 mM) > GLY (IC50 > >1 mM, both cell lines), after 24 h treatment, being toxicity time-dependent (lower IC50 values at 48 h). Toxicity is explained by oxidative stress, as IMZ induced a higher intracellular ROS increase and lipid peroxidation, followed by IMD, while GLY did not change these markers. However, the three pesticides induced loss of MMP in HepG2 cells while in Caco-2 cells only IMZ produced significant MMP loss. Increased ROS and loss of MMP promoted apoptosis in Caco-2 cells subjected to IMZ, and in HepG2 cells exposed to IMD and IMZ, as assessed by Annexin-V/PI. The toxicity profile of pesticides is directly correlated with their Log Pow, as affinity for the lipophilic environment favours interaction with cell membranes governs, and is inversely correlated with their TPSA; however, membrane permeation is favoured by lower TPSA. IMZ presents the best molecular properties for membrane interaction and cell permeation, i.e., higher Log Pow, lower TPSA and lower hydrogen-bond (H-bond) donor/acceptor correlating with its higher toxicity. In conclusion, molecular physicochemical factors such as Log Pow, TPSA, and H-bond are likely to be directly correlated with pesticide-induced toxicity, thus they are key factors to potentially predict the toxicity of other compounds.

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Section: Introductionmentioning

confidence: 99%

Molecular Physicochemical Properties of Selected Pesticides as Predictive Factors for Oxidative Stress and Apoptosis-Dependent Cell Death in Caco-2 and HepG2 Cells

Silva

Martins-Gomes

Ferreira

et al. 2022

IJMS

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“…In line with the above, it has been widely demonstrated that pesticide exposure favors ROS production and, with it, oxidative stress conditions [159,182,183]. ROS can modulate the activity of a wide variety of Ca 2+ channels, pumps, and exchangers.…”

Section: Discussionmentioning

confidence: 83%

Systematic Review of Calcium Channels and Intracellular Calcium Signaling: Relevance to Pesticide Neurotoxicity

Costas-Ferreira

Faro

2021

IJMS

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Pesticides of different chemical classes exert their toxic effects on the nervous system by acting on the different regulatory mechanisms of calcium (Ca2+) homeostasis. Pesticides have been shown to alter Ca2+ homeostasis, mainly by increasing its intracellular concentration above physiological levels. The pesticide-induced Ca2+ overload occurs through two main mechanisms: the entry of Ca2+ from the extracellular medium through the different types of Ca2+ channels present in the plasma membrane or its release into the cytoplasm from intracellular stocks, mainly from the endoplasmic reticulum. It has also been observed that intracellular increases in the Ca2+ concentrations are maintained over time, because pesticides inhibit the enzymes involved in reducing its levels. Thus, the alteration of Ca2+ levels can lead to the activation of various signaling pathways that generate oxidative stress, neuroinflammation and, finally, neuronal death. In this review, we also discuss some proposed strategies to counteract the detrimental effects of pesticides on Ca2+ homeostasis.

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“…This is biologically plausible as polymorphisms in paraoxonase 1, an enzyme that detoxifies organophosphates,31 have been associated with the development of ALS,32 and high exposure to organophosphates can result in OP-induced delayed neuropathy, a condition akin to ALS 14. Organophosphates also induce oxidative stress,33 which plays an important role in the pathogenesis of MND 34. We observed an elevated MND risk from exposure to pyrethroids insecticides, which is consistent with an earlier case report that presented a patient who developed MND after 3 years of chronic exposure to pyrethroids 35.…”

Section: Discussionmentioning

confidence: 99%

Occupational exposures to pesticides and other chemicals: a New Zealand motor neuron disease case–control study

et al. 2022

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ObjectivesTo assess associations between occupational exposures to pesticides and other chemicals and motor neuron disease (MND).MethodsA population-based case–control study that included 319 MND cases (64% male/36% female) recruited through the New Zealand MND Association complemented with hospital discharge data, and 604 controls identified from the Electoral Roll. For each job held, a questionnaire collected information on 11 exposure categories (dust, fibres, tobacco smoke, fumes, gas, fumigants, oils/solvents, acids/alkalis, pesticides, other chemicals and animals/animal products). ORs were estimated using logistic regression adjusting for age, sex, ethnicity, socioeconomic status, education, smoking, alcohol consumption, physical activities, head/spine injury and other occupational exposures.ResultsTwo exposure categories were associated with increased MND risks: pesticides (OR 1.70, 95% CI 1.17 to 2.48) and fumigants (OR 3.98, 95% CI 1.81 to 8.76), with risks increasing with longer exposure duration (p<0.01). Associations were also observed for: methyl bromide (OR 5.28, 95% CI 1.63 to 17.15), organochlorine insecticides (OR 3.28, 95% CI 1.18 to 9.07), organophosphate insecticides (OR 3.11, 95% CI 1.40 to 6.94), pyrethroid insecticides (OR 6.38, 95% CI 1.13 to 35.96), inorganic (copper) fungicides (OR 4.66, 95% CI 1.53 to 14.19), petrol/diesel fuel (OR 2.24, 95% CI 1.27 to 3.93) and unspecified solvents (OR 1.91, 95% CI 1.22 to 2.99). In women, exposure to textile fibres (OR 2.49, 95% CI 1.13 to 5.50), disinfectants (OR 9.66, 95% CI 1.29 to 72.44) and cleaning products (OR 3.53, 95% CI 1.64 to 7.59) were also associated with MND; this was not observed in men (OR 0.80, 95% CI 0.44 to 1.48; OR 0.72, 95% CI 0.29 to 1.84; OR 0.57, 95% CI 0.21 to 1.56, respectively).ConclusionsThis study adds to the evidence that pesticides, especially insecticides, fungicides, and fumigants, are risk factors for MND.

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Oxidative stress and DNA damage in agricultural workers after exposure to pesticides

Cited by 49 publications

References 46 publications

Molecular Physicochemical Properties of Selected Pesticides as Predictive Factors for Oxidative Stress and Apoptosis-Dependent Cell Death in Caco-2 and HepG2 Cells

Molecular Physicochemical Properties of Selected Pesticides as Predictive Factors for Oxidative Stress and Apoptosis-Dependent Cell Death in Caco-2 and HepG2 Cells

Systematic Review of Calcium Channels and Intracellular Calcium Signaling: Relevance to Pesticide Neurotoxicity

Occupational exposures to pesticides and other chemicals: a New Zealand motor neuron disease case–control study

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