Oxidative stress and genotoxicity of co-exposure to chlorpyrifos and aflatoxin B₁ in HepG2 cells

Abstract

<jats:p> Chlorpyrifos (CPF) and aflatoxin B<jats:sub>1</jats:sub> (AFB<jats:sub>1</jats:sub>) are each known to adversely affect hepatic tissue individually, but their combined hepatic effects have never been previously investigated. HepG2 cell viability, oxidative status, and genetic impairment were examined after exposing HepG2 cells to: (1) CPF alone, (2) AFB<jats:sub>1</jats:sub> alone, and (3) CPF and AFB<jats:sub>1</jats:sub> combined (20:1). CPF exposure decreased cell viability, reduced glutathione (GSH) content, and superoxide dismutase (SOD) activity but increased both glutathione peroxidase (GPx) and paraoxonase 1 activity. AFB<jats:sub>1</jats:sub> exposure decreased cell viability and GSH content but increased reactive oxygen species (ROS) production. CPF and AFB<jats:sub>1</jats:sub> combined exposure decreased GSH content ( p &lt; 0.05) further over individual CPF and AFB<jats:sub>1</jats:sub> exposures. Induction of micronucleus formation was detected in AFB<jats:sub>1</jats:sub>-treated cells but undetected in both CPF and combination-treated cells. In conclusion, cytotoxic effects caused by combined exposure were antagonistic, as shown by a combination index value of 1.67. Although no change in ROS production was observed in CPF groups, the overall results confirmed the occurrence of oxidative stress through the alterations of GSH content, GPx, and SOD activity. Only intracellular GSH was evidently changed upon exposure to CPF and AFB<jats:sub>1</jats:sub> combined. Thus, this study suggested cellular GSH as a potential indicator for detecting the combined effects of CPF and AFB<jats:sub>1</jats:sub> in HepG2 cells, the detection of which could be adapted to estimate the potential toxicity of additional multiple toxicant exposures. </jats:p>

Pterostilbene Alleviates Chlorpyrifos-Induced Damage During Porcine Oocyte Maturation

“…ROS and GSH are also known as the key markers to regulate the intracellular redox balance and evaluate oocyte cytoplasmic maturation. Here, ROS and GSH were applied to investigate the effect of CPF on oocyte maturation, and CPF was shown to significantly increase ROS and decrease GSH, suggesting that CPF impairs oocyte cytoplasmic maturation by destroying the balance between ROS and GSH, similar with the previous studies in cells (Chiapella et al, 2013;Tadee et al, 2020). The antioxidant molecules have been shown to eliminate free radicals and protect cells against oxidative damage.…”

Changes in Oxidative Stress Parameters in Terms of Simultaneous Exposure to Physical and Chemical Factors: A Systematic Review

“…Stress is the reaction of the organism’s nervous and endocrine systems to environmental demands or pressures. The body tries to limit stress if a stressor persists, the body concentrates resources and resists the stress and remains in a state of alertness ( 15 , 19 , 20 ). Oxidative stress occurs in cells when there is an imbalance in the production of oxidants or reactive oxygen species (ROS) and their ability to be removed by endogenous antioxidants ( 21 ).…”

“…They are associated with aberrant lung processes and asthmatic infections and may easily penetrate human lung tissue by inhalation. In young people, exposure to high concentrations of PAHs and BTs is associated with increased oxidative damage and impaired lung function ( 15 ). Similar to this study, children with asthma may have higher levels of oxidative lipid and DNA damage as well as airway inflammation after exposure to PAHs and BTs together ( 38 ).…”

Aflatoxins: History, Significant Milestones, Recent Data on Their Toxicity and Ways to Mitigation

“…The genotoxic effect has been observed in vivo on mice [110]. Cytotoxic and/or genotoxic effects of AFB 1 have been reported in vitro on the leghorn male hepatoma (LMH) cell line [121], the liver hepatocellular carcinoma (HepG2) cell line [122], buffalo rat liver (BRL-3A) cells [123], bovine mammary epithelial (BME) cells [124], and the human keratinocyte (HaCaT) cell line [125]. Cytotoxicity on BME cells has also been observed in vitro in the case of AFM 1 [124].…”

“…Therefore, due to their co-occurrence, it is necessary to consider their combined toxic effects. Recently, an antagonistic interaction between AFB 1 and the insecticide chlorpyrifos has been observed on HepG2 cells for cytotoxicity and genotoxicity [122]. In the case of AFB 1 and insecticide p,p'-DDT, a dose-dependent interaction has been observed on MA-10 Leydig cells in vitro-additive at doses of 16 µM (5671.84 µg/L and 4996.36 µg/L of p,p'-DDT and AFB 1 , respectively) and 32 µM (11,343.68 µg/L and 9992.64 µg/L of p,p'-DDT and AFB 1 , respectively) and antagonistic at 64 µM (22,687.36 µg/L and 19,985.28 µg/L of p,p'-DDT and AFB 1 , respectively) [134].…”