Organochlorine pesticides induce inflammation, ROS production, and DNA damage in human epithelial ovary cells: An in vitro study

Shah, Harendra K.; Sharma, T.; Banerjee, Basu Dev

doi:10.1016/j.chemosphere.2019.125691

Cited by 68 publications

(46 citation statements)

References 77 publications

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“…A recently published article provided evidence that 20 µM β-HCH can induce a substantial ROS increase in HOSE ovary cells [26]. To confirm this outcome, ROS production was quantified by performing CellRox assay on both LNCaP and HepG2 cells treated with 10 µM β-HCH for 6 h. Values listed in Figure 8 evidence a significant intensification of the fluorescence after β-HCH stimulation, thus indicating an enhanced ROS production.…”

Section: Oxidative Stress and Energy Metabolismmentioning

confidence: 86%

β-Hexachlorocyclohexane: A Small Molecule with a Big Impact on Human Cellular Biochemistry

et al. 2020

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Organochlorine pesticides (OCPs) belong to a heterogeneous class of organic compounds blacklisted by the Stockholm Convention in 2009 due to their harmful impact on human health. Among OCPs, β-hexachlorocyclohexane (β-HCH) is one of the most widespread and, at the same time, poorly studied environmental contaminant. Due to its physicochemical properties, β-HCH is the most hazardous of all HCH isomers; therefore, clarifying the mechanisms underlying its molecular action could provide further elements to draw the biochemical profile of this OCP. For this purpose, LNCaP and HepG2 cell lines were used as models and were subjected to immunoblot, immunofluorescence, and RT-qPCR analysis to follow the expression and mRNA levels, together with the distribution, of key biomolecules involved in the intracellular responses to β-HCH. In parallel, variations in redox homeostasis and cellular bioenergetic profile were monitored to have a complete overview of β-HCH effects. Obtained results strongly support the hypothesis that β-HCH could be an endocrine disrupting chemical as well as an activator of AhR signaling, promoting the establishment of an oxidative stress condition and a cellular metabolic shift toward aerobic glycolysis. In this altered context, β-HCH can also induce DNA damage through H2AX phosphorylation, demonstrating its multifaceted mechanisms of action.

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Section: Oxidative Stress and Energy Metabolismmentioning

confidence: 86%

β-Hexachlorocyclohexane: A Small Molecule with a Big Impact on Human Cellular Biochemistry

et al. 2020

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“…Ã p < 0.05, ÃÃ p < 0.01, compared with the control; # p < 0.05, ## p < 0.01, compared with the PCB52 group. Full-size  DOI: 10.7717/peerj.9720/ fig-4 Notably, the overproduction of ROS promotes the release of inflammatory mediators, including TNF-a and IL-1β, via activation of the TLR4/MyD88 pathway (Gong et al, 2019;Shah, Sharma & Banerjee, 2019;Steckling et al, 2020). The transmembrane protein TLR4 is a vital member of the toll-like receptor family, and its interaction with the adaptors MyD88 and TRAF6 are essential for activation of downstream elements and induction of inflammatory response (Dasu & Jialal, 2013).…”

Section: Discussionmentioning

confidence: 99%

N-acetylcysteine alleviates PCB52-induced hepatotoxicity by repressing oxidative stress and inflammatory responses

Zhou

Wang

et al. 2020

PeerJ

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Polychlorinated biphenyls (PCBs), particularly low chlorinated congeners in our environment, can induce human hepatotoxicity. However, the mechanisms by which PCBs cause hepatotoxicity remain elusive. Moreover, there are no effective treatments for this condition. In this study, 40 μM PCB52 was administered to rat (Brl-3A) and human hepatocytes (L-02) for 48 h following the N-acetylcysteine (NAC)/saline pretreatment. A significant decrease in cell viability was observed in PCB52-treated cells relative to the control. Besides, PCB52 significantly increased reactive oxygen species (ROS) levels and malondialdehyde (MDA) contents, suggesting induction of oxidative stress. The expression of Traf6, MyD88, and Tnf in Brl-3A cells and that of MYD88, TNF, and IL1B in L-02 cells were significantly upregulated by PCB52. Consistently, overexpression of TLR4, MyD88, Traf6, and NF-κB p65 proteins was observed in PCB52-treated cells, indicating activation of inflammatory responses. Nevertheless, no changes in kelch-like ECH-associated protein 1 (keap1), nuclear factor-erythroid 2-related factor (nrf2), and heme oxygenase-1 proteins were observed in PCB52-treated cells, indicating non-activation of the keap1/nrf2 pathway. Pretreatment with NAC significantly ameliorated PCB52 effects on cell viability, ROS levels, MDA contents and expression of inflammatory elements at both RNA and protein levels. However, no changes in keap1, nrf2 and HO-1 protein levels were detected following NAC pretreatment. Taken together, with non-activated keap1/nrf2 pathway, PCB52-induced oxidative stress and inflammatory responses could be responsible for its hepatotoxicity. These effects were effectively attenuated by NAC pretreatment, which scavenges ROS and dampens inflammatory responses. This study might provide novel strategies for the treatment of the PCBs-associated hepatotoxic effects.

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“…Pesticides such as OCs are known to be genotoxic and induce DNA damage [119,120], either via oxidative damage [121] or direct interaction [122] with DNA. Pesticide genotoxicity is usually considered in the context of their oncogenic potential [123,124], particularly during episodes of acute exposure with mutational damage to dividing cells, such as neural stem cells (NSCs) and neural progenitor cells (NPCs).…”

Section: Dna Damage and Somatic Mutationsmentioning

confidence: 99%

Neuropathological Mechanisms Associated with Pesticides in Alzheimer’s Disease

Tang

2020

Toxics

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Environmental toxicants have been implicated in neurodegenerative diseases, and pesticide exposure is a suspected environmental risk factor for Alzheimer’s disease (AD). Several epidemiological analyses have affirmed a link between pesticides and incidence of sporadic AD. Meanwhile, in vitro and animal models of AD have shed light on potential neuropathological mechanisms. In this paper, a perspective on neuropathological mechanisms underlying pesticides’ induction of AD is provided. Proposed mechanisms range from generic oxidative stress induction in neurons to more AD-specific processes involving amyloid-beta (Aβ) and hyperphosphorylated tau (p-tau). Mechanisms that are more speculative or indirect in nature, including somatic mutation, epigenetic modulation, impairment of adult neurogenesis, and microbiota dysbiosis, are also discussed. Chronic toxicity mechanisms of environmental pesticide exposure crosstalks in complex ways and could potentially be mutually enhancing, thus making the deciphering of simplistic causal relationships difficult.

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Organochlorine pesticides induce inflammation, ROS production, and DNA damage in human epithelial ovary cells: An in vitro study

Cited by 68 publications

References 77 publications

β-Hexachlorocyclohexane: A Small Molecule with a Big Impact on Human Cellular Biochemistry

β-Hexachlorocyclohexane: A Small Molecule with a Big Impact on Human Cellular Biochemistry

N-acetylcysteine alleviates PCB52-induced hepatotoxicity by repressing oxidative stress and inflammatory responses

Neuropathological Mechanisms Associated with Pesticides in Alzheimer’s Disease

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