Acute exposure to chlorpyrifos caused NADPH oxidase mediated oxidative stress and neurotoxicity in a striatal cell model of Huntington’s disease

Dominah, Gifty; McMinimy, Rachael; Kallon, Sallay; Kwakye, Gunnar F.

doi:10.1016/j.neuro.2017.03.004

Cited by 29 publications

(9 citation statements)

References 69 publications

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“…Betanin (a natural pigment) can decrease the CPF-induced increase in ROS formation to reduce hepatotoxicity in the primary rat hepatocytes [49]. Cotreatment with apocynin (a NADPH oxidase inhibitor) blunted the generation of ROS and the neurotoxicity induced by CPF [50]. Our results are consistent with these findings because CPF exposure induced an increase in the ROS levels.…”

Section: Discussionsupporting

confidence: 88%

Chlorpyrifos Suppresses Neutrophil Extracellular Traps in Carp by Promoting Necroptosis and Inhibiting Respiratory Burst Caused by the PKC/MAPK Pathway

Zhang

Wang

Zheng

et al. 2019

Oxidative Medicine and Cellular Longevity

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Neutrophil extracellular traps (NETs) are reticular structures formed by myeloperoxidase (MPO), histones, and neutrophil elastase (NE) that are released from neutrophils in response to pathogenic stimuli. Chlorpyrifos (CPF) is wildly used as an organophosphorus pesticide that causes a range of toxicological and environmental problems. Exposure to CPF can increase the production of neutrophils in carps, and this increase can be considered a biomarker of water pollution. To explore a relationship between NETs and CPF and its mechanism of influence, we treated neutrophils from the blood of carp with 1 μg/mL phorbol 12-myristate 13-acetate (PMA), 0.325 mg/L CPF, or 20 μM necrostatin-1 (Nec-1). The production of MPO and NETs was reduced in the CPF+PMA group compared with that in the PMA group. CPF can cause an increase in reactive oxygen species (ROS), while inhibiting respiratory burst caused by PMA stimulation. We found that the expression levels of protein-coupled receptor 84 (gpr84), dystroglycan (DAG), proto-oncogene serine/threonine kinase (RAF), protein kinase C (PKC), and mitogen-activated protein kinase 3 (MAPK3) in the CPF+PMA group were lower than those in the PMA group, indicating that the PKC-MAPK pathway was suppressed. The expression levels of cylindromatosis (CYLD), mixed lineage kinase domain-like pseudokinase (MLKL), receptor-interacting serine-threonine kinase 1 (RIP1), and receptor-interacting serine-threonine kinase 3 (RIP3) were increased, and the expression levels of caspase 8 were reduced by CPF, indicating that CPF may cause necroptosis. The addition of Nec-1 restored the number of NETs in the CPF+PMA group. The results indicate that CPF reduced the production of NETs by inhibiting respiratory burst and increasing necroptosis. The results contribute to the understanding of the immunotoxicological mechanism of CPF and provide a reference for comparative medical studies.

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Section: Discussionsupporting

confidence: 88%

Chlorpyrifos Suppresses Neutrophil Extracellular Traps in Carp by Promoting Necroptosis and Inhibiting Respiratory Burst Caused by the PKC/MAPK Pathway

Zhang

Wang

Zheng

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…H 2 O 2 can interact with mutant huntingtin in the brain of HD patients [147]. The activity of NOX can be measured by lucigenin-enhanced luminescence method [148]. The heterozygous huntingtin (HTT) and Cd can induce cytotoxicity which will cause NOXs-mediated oxidative stress.…”

Section: Nadph-and Nox-mediated Oxidative Stressmentioning

confidence: 99%

Targeting Molecular Mediators of Ferroptosis and Oxidative Stress for Neurological Disorders

Jia

Cheng

et al. 2022

Oxidative Medicine and Cellular Longevity

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With the acceleration of population aging, nervous system diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), anxiety, depression, stroke, and traumatic brain injury (TBI) have become a huge burden on families and society. The mechanism of neurological disorders is complex, which also lacks effective treatment, so relevant research is required to solve these problems urgently. Given that oxidative stress-induced lipid peroxidation eventually leads to ferroptosis, both oxidative stress and ferroptosis are important mechanisms causing neurological disorders, targeting mediators of oxidative stress and ferroptosis have become a hot research direction at present. Our review provides a current view of the mechanisms underlying ferroptosis and oxidative stress participate in neurological disorders, the potential application of molecular mediators targeting ferroptosis and oxidative stress in neurological disorders. The target of molecular mediators or agents of oxidative stress and ferroptosis associated with neurological disorders, such as reactive oxygen species (ROS), nuclear factor erythroid 2–related factor-antioxidant response element (Nrf2-ARE), n-acetylcysteine (NAC), Fe2+, NADPH, and its oxidases NOX, has been described in this article. Given that oxidative stress-induced ferroptosis plays a pivotal role in neurological disorders, further research on the mechanisms of ferroptosis caused by oxidative stress will help provide new targets for the treatment of neurological disorders.

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“…Bats exposed to CPF showed upregulation of NOX3 after three days of exposure, which also corresponded to their worst performance in the associative memory test. Overexpression of NOX3, exacerbated by CPF exposure [84], can lead to hearing loss [85,86] and balance disorders due to the induction of reactive oxygen species (ROS), which causes neuronal loss in the central auditory system.…”

Section: Discussionmentioning

confidence: 99%

Common insecticide affects spatial navigation in bats at environmentally-realistic doses

Herrera

Jacobo

Soto

et al. 2022

Preprint

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Bats are potentially exposed to pesticides via foraging in croplands. Common pesticides like organophosphates are neurotoxic for vertebrates and even low doses can impair essential processes such as locomotion and cognition. These sublethal effects are usually studied using molecular biomarkers with limited ecological relevance. Behavioral studies, in contrast, represent a more informative yet sensitive approach. Spatial navigation, for example, is an ecologically relevant behavior that is modulated by cellular pathways potentially targeted by neurotoxicants. We evaluated whether bats’ ability to memorize and navigate novel spaces was negatively affected by environmental relevant doses of chlorpyrifos, a common organophosphate insecticide. We also tested how the behavioral response correlated with molecular biomarkers. We orally dosed captive big brown bats (Eptesicus fuscus) with chlorpyrifos and studied exploratory behavior in two testing arenas. We evaluated similarity of stereotype flight trajectories in a flight tent, and associative memory in a Y-maze. We quantified brain cholinesterase (ChE) activity as a cellular biomarker and employed non-targeted proteomics as molecular biomarkers. Bats exposed to chlorpyrifos were less explorative and made more incorrect choices in the Y-maze, but the consistency of their flight trajectories was unaffected. Exposed bats had 30% lower ChE activity, showed down-regulation of proteins involved in memory (VP37D), learning and sound perception (NOX3). Other important nervous system processes such as synaptic function, plasticity, oxidative stress, and apoptosis were enriched in chlorpyrifos-exposed bats. These results support the sensitivity of behavior as a biomarker of toxicity and the importance of considering other levels of organization to help explain the mechanisms underlying altered behavior due to human activities.

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Acute exposure to chlorpyrifos caused NADPH oxidase mediated oxidative stress and neurotoxicity in a striatal cell model of Huntington’s disease

Cited by 29 publications

References 69 publications

Chlorpyrifos Suppresses Neutrophil Extracellular Traps in Carp by Promoting Necroptosis and Inhibiting Respiratory Burst Caused by the PKC/MAPK Pathway

Chlorpyrifos Suppresses Neutrophil Extracellular Traps in Carp by Promoting Necroptosis and Inhibiting Respiratory Burst Caused by the PKC/MAPK Pathway

Targeting Molecular Mediators of Ferroptosis and Oxidative Stress for Neurological Disorders

Common insecticide affects spatial navigation in bats at environmentally-realistic doses

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