Malathion‐induced oxidative stress, cytotoxicity, and genotoxicity in human liver carcinoma (HepG₂) cells

Abstract

Malathion is an organophosphate pesticide that is known for its high toxicity to insects and low to moderate potency to humans and other mammals. Its toxicity has been associated with the inhibition of acetylcholinesterase activity, leading to the interference with the transmission of nerve impulse, accumulation of acetylcholine at synaptic junctions, and subsequent induction of adverse health effects including headache, dizziness, nausea, vomiting, bradycardia, and miosis. Oxidative stress (OS) has been reported as a possible mechanism of malathion toxicity in humans. Hence, the aim of the present study was to examine the role of OS in malathion-induced cytotoxicity and genotoxicity. To achieve this goal, MTT, lipid peroxidation, and single cell gel electrophoresis (Comet) assays were performed, respectively to evaluate the levels of cell viability, malondialdehyde (MDA) production, and DNA damage in human liver carcinoma (HepG 2 ) cells. Study results indicated that malathion is mitogenic at lower levels of exposure, and cytotoxic at higher levels of exposure. Upon 48 h of exposure, the average percentages of cell viability were 100±11%, 117±15%, 86±15%, 35 ±9%, and 27±7% for 0, 6, 12, 18, and 24 mM, respectively. In the lipid peroxidation assay, the concentrations of MDA produced were 12.55±0. 16, 20.65±0.27, 31.1±0.40, 34.75±0.45, and 15.1 ±0.20 μM in 0, 6, 12, 18, and 24 mM of malathion, respectively. The Comet assay showed a significant increase in DNA damage at the 24mM malathion exposure. Taken together, our results indicate that malathion exposure at higher concentrations induces cytotoxic and genotoxic effects in HepG 2 cells, and its toxicity may be mediated through oxidative stress as evidenced by a significant production of MDA, an end product of lipid peroxidation.

Application of primary haemocyte culture of Penaeus monodon in the assessment of cytotoxicity and genotoxicity of heavy metals and pesticides

“…Cytotoxicity increased with concentration for both the pesticides, and malathion was more toxic when compared to monocrotophos. Similarly, concentration dependant increase in the toxicity of malathion was detected in grass carp cell line (Chen et al, 2006) and human liver carcinoma cell line (Moore et al, 2010). IC 50 of malathion ranged from 37.94 AE 1.93 mg l À1 for 12 h to 3.04 AE 0.27 mg l À1 for 72 h in grass carp cells (Chen et al, 2006).…”

Evaluation of genotoxicity by comet assay (single-cell gel electrophoresis) in tissues of the fish Cyprinus carpio during sub-lethal exposure to Karanjin

“…Studies conducted by Chandra and Khuda-Bukhsh (2004) and Klopman, Conttreras, Reosenkranz, and Waters, (1985) showed that during the metabolism of azadirachtin, electrophilic ions and free radicals are produced, which interact with the nucleophilic sites in DNA and lead to breaks and other related DNA damage. It is also reported that the oxidative stress in an organism plays an important role to inducing cytotoxicity and genotoxicity in different vital tissues (Moore, Yedjou, & Tchounwou, 2010).…”

Adverse effects of organophosphorus pesticides on the liver: a brief summary of four decades of research

“…OPs are oxidants and impair enzymatic antioxidant defences, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) (23,34,44,(114)(115)(116)(117)(118)(119)(120)(121)(122)(123)(124)(125)(126)(127)(128)(129). Malathion, methyl parathion, and parathion in HepG2 cell lines, as well as chlorpyrifos, methidathion, chlorfenvinphos, and dimethoate in rat liver and diazinon in fish most probably disrupt membrane lipids through oxidative stress (23,35,61,116,118,(130)(131)(132)(133)(134)(135). Table 1 summarises the key changes in antioxidant defence and oxidative stress biomarkers caused by OPs.…”

“…The mutagenic effects of OPs are owed to the direct alkylating ability of the parental molecule and its metabolites (130,131,155).…”

“…Several in vivo and in vitro studies reported that the genotoxicity of OPs such as dimethoate, methyl parathion, chlorpyrifos, phorate, and malathion in hepatocytes was associated with oxidative damage (130,131,127,(149)(150)(151)(152)(153)(154)(155)(156)(157)(158)(159). A study by Hreljac et al (160) showed that methyl paraoxon was less genotoxic in HepG2 cells than its parent OP methyl parathion.…”