Arsenic trioxide mediates HAPI microglia inflammatory response and the secretion of inflammatory cytokine IL-6 via Akt/NF-κB signaling pathway

Chen, Gang; Mao, Jiamin; Zhao, Jingbo; Zhang, Yan; Li, Ting; Wang, Cheng; Xu, Lingfei; Hu, Qiaoyun; Wang, Xiaoke; Jiang, Shengyang; Nie, Xiaobing; Wu, Qianhui

doi:10.1016/j.yrtph.2016.09.027

Cited by 29 publications

(4 citation statements)

References 52 publications

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“…In addition to the micro structural changes in the brain, arsenic exposure also affects neuronal system at the cellular levels. Arsenic significantly affects the neuronal, glial, and astrocyte components of the brain [157,158]. The neurotoxic effects of arsenic are mediated through the oxidative stress and mitochondria dysfunction [152,159] (Table 4).…”

Section: Arsenic (As)mentioning

confidence: 99%

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

Patwa

Flora

2020

IJMS

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Heavy metals are considered a continuous threat to humanity, as they cannot be eradicated. Prolonged exposure to heavy metals/metalloids in humans has been associated with several health risks, including neurodegeneration, vascular dysfunction, metabolic disorders, cancer, etc. Small blood vessels are highly vulnerable to heavy metals as they are directly exposed to the blood circulatory system, which has comparatively higher concentration of heavy metals than other organs. Cerebral small vessel disease (CSVD) is an umbrella term used to describe various pathological processes that affect the cerebral small blood vessels and is accepted as a primary contributor in associated disorders, such as dementia, cognitive disabilities, mood disorder, and ischemic, as well as a hemorrhagic stroke. In this review, we discuss the possible implication of heavy metals/metalloid exposure in CSVD and its associated disorders based on in-vitro, preclinical, and clinical evidences. We briefly discuss the CSVD, prevalence, epidemiology, and risk factors for development such as genetic, traditional, and environmental factors. Toxic effects of specific heavy metal/metalloid intoxication (As, Cd, Pb, Hg, and Cu) in the small vessel associated endothelium and vascular dysfunction too have been reviewed. An attempt has been made to highlight the possible molecular mechanism involved in the pathophysiology, such as oxidative stress, inflammatory pathway, matrix metalloproteinases (MMPs) expression, and amyloid angiopathy in the CSVD and related disorders. Finally, we discussed the role of cellular antioxidant defense enzymes to neutralize the toxic effect, and also highlighted the potential reversal strategies to combat heavy metal-induced vascular changes. In conclusion, heavy metals in small vessels are strongly associated with the development as well as the progression of CSVD. Chelation therapy may be an effective strategy to reduce the toxic metal load and the associated complications.

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Section: Arsenic (As)mentioning

confidence: 99%

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

Patwa

Flora

2020

IJMS

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“…Recent studies have shown that arsenic alters the functions of microglia, which are the resident macrophages found in the central nervous system [12,13]. The metalloid notably increased ex-vivo secretion of IL-6 and TNF- from microglia isolated from mice exposed for 7 days to 0.38 mg/kg arsenite [12].…”

Section: Macrophages and Dendritic Cells (Dcs)mentioning

confidence: 99%

Arsenic and the immune system

Bellamri

Morzadec

Fardel

et al. 2018

Current Opinion in Toxicology

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Arsenic is a metalloid to which millions of individuals are exposed worldwide, primarily through the consumption of contaminated drinking water or food items. Chronic arsenic exposure is associated with an increased incidence of several diseases, including lung infections and skin cancers. Epidemiological and experimental evidence demonstrates that the metalloid impairs the activity of both the innate and adaptive immune systems. Arsenic alters the differentiation, activation and/or proliferation of human macrophages, dendritic cells and T lymphocytes. Arsenic immunotoxicity results from intracellular oxidative lesions modulating basal gene expression or leading to DNA damage. Arsenic also induces epigenetic effects by modulating DNA methylation and post-translational histone modifications. In addition, the metalloid has recently been found to inhibit in vitro and in vivo inflammasome activities. Arsenic immunotoxicity likely contributes to the systemic effects associated with arsenic exposure by limiting immune surveillance and/or promoting inflammation. Experimental studies also suggest that the immunosuppressive effects of arsenic efficiently prevent or treat severe immune-related diseases. The purpose of this review is to summarize the current knowledge of the impact of arsenic on the immune system.

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“…On the other hand, even though As at nanomolar concentrations does not affect the viability of microglial cells, the innate immune component of the brain, it can activate the c-Jun N-terminal kinase (JNK)/signal transducer and activator of transcription (STAT)3/nuclear factor-κB (NF-κB) in these cells, increasing the production of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α), reducing phagocytic activity and increasing the expression of Iba-1, a microglial activation marker [264][265][266][267]. The As-mediated effects on astrocytes and microglia have repercussions on neuronal viability, it has been reported that neurons incubated with conditioned mediums of Astreated astrocytes had fewer presynaptic terminals, as well as a decreased expression of the NMDAR subunits NR1, NR2A, and NR2B and reduced levels of adenylyl cyclase and Calcium/calmodulin-dependent protein kinase III (CaMKIII) [268].…”

Section: Neurochemical Dysfunction Induced By Arsenic Exposurementioning

confidence: 99%

Mechanisms Associated with Cognitive and Behavioral Impairment Induced by Arsenic Exposure

Vázquez Cervantes,

González Esquivel,

Ramírez Ortega

et al. 2023

Cells

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Arsenic (As) is a metalloid naturally present in the environment, in food, water, soil, and air; however, its chronic exposure, even with low doses, represents a public health concern. For a long time, As was used as a pigment, pesticide, wood preservative, and for medical applications; its industrial use has recently decreased or has been discontinued due to its toxicity. Due to its versatile applications and distribution, there is a wide spectrum of human As exposure sources, mainly contaminated drinking water. The fact that As is present in drinking water implies chronic human exposure to this metalloid; it has become a worldwide health problem, since over 200 million people live where As levels exceed safe ranges. Many health problems have been associated with As chronic exposure including cancer, cardiovascular diseases, gastrointestinal disturbances, and brain dysfunctions. Because As can cross the blood–brain barrier (BBB), the brain represents a target organ where this metalloid can exert its long-term toxic effects. Many mechanisms of As neurotoxicity have been described: oxidative stress, inflammation, DNA damage, and mitochondrial dysfunction; all of them can converge, thus leading to impaired cellular functions, cell death, and in consequence, long-term detrimental effects. Here, we provide a current overview of As toxicity and integrated the global mechanisms involved in cognitive and behavioral impairment induced by As exposure show experimental strategies against its neurotoxicity.

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Arsenic trioxide mediates HAPI microglia inflammatory response and the secretion of inflammatory cytokine IL-6 via Akt/NF-κB signaling pathway

Cited by 29 publications

References 52 publications

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

Arsenic and the immune system

Mechanisms Associated with Cognitive and Behavioral Impairment Induced by Arsenic Exposure

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