Neurotoxic Mechanism of Arsenic: Synergistic Effect of Mitochondrial Instability, Oxidative Stress, and Hormonal-Neurotransmitter Impairment

Medda, Nandita; Patra, R C; Ghosh, Tamal; Maiti, Smarajit

doi:10.1007/s12011-020-02044-8

Cited by 58 publications

(29 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neuroinflammation is another crucial event that largely contributes to AD pathobiology [ 43 ]. Evidence suggests that arsenic plays a vital role in neuroinflammation via activation of microglia through secretion of pro-inflammatory cytokines, which could damage cognitive function, intellectual ability, and learning and memory functions [ 11 , 44 ]. Arsenic administration augmented ROS-mediated expression of pro-inflammatory cytokines in rats via activation of MAP kinase and protein kinase C through increased mRNA levels of pro-inflammatory markers such as TNFα, IL-1β, and IFNγ with protein expression of TNFα and IFNγ [ 45 ].…”

Section: Molecular Basis Of Arsenic Toxicity and Its Implication In Ad Pathobiologymentioning

confidence: 99%

“…Arsenic has shown its mutagenic response via disruption of mitochondrial function. As-induced perturbation to mitochondrial oxidation caused production of excess superoxide anions, which when reacted with nitric oxide generate highly reactive peroxynitrites [ 44 ]. Arsenic toxicity affects the mitochondrial membrane potential via generating ROS and DNA fragmentation, and ROS overproduction is associated with apoptosis induction by the release of cytochrome c, which activates the caspase pathway ( Figure 4 ) [ 51 ].…”

Section: Molecular Basis Of Arsenic Toxicity and Its Implication In Ad Pathobiologymentioning

confidence: 99%

See 1 more Smart Citation

Exposure to Environmental Arsenic and Emerging Risk of Alzheimer’s Disease: Perspective Mechanisms, Management Strategy, and Future Directions

Rahman

Hannan

Uddin

et al. 2021

Toxics

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is one of the most prevailing neurodegenerative diseases, characterized by memory dysfunction and the presence of hyperphosphorylated tau and amyloid β (Aβ) aggregates in multiple brain regions, including the hippocampus and cortex. The exact etiology of AD has not yet been confirmed. However, epidemiological reports suggest that populations who were exposed to environmental hazards are more likely to develop AD than those who were not. Arsenic (As) is a naturally occurring environmental risk factor abundant in the Earth’s crust, and human exposure to As predominantly occurs through drinking water. Convincing evidence suggests that As causes neurotoxicity and impairs memory and cognition, although the hypothesis and molecular mechanism of As-associated pathobiology in AD are not yet clear. However, exposure to As and its metabolites leads to various pathogenic events such as oxidative stress, inflammation, mitochondrial dysfunctions, ER stress, apoptosis, impaired protein homeostasis, and abnormal calcium signaling. Evidence has indicated that As exposure induces alterations that coincide with most of the biochemical, pathological, and clinical developments of AD. Here, we overview existing literature to gain insights into the plausible mechanisms that underlie As-induced neurotoxicity and the subsequent neurological deficits in AD. Prospective strategies for the prevention and management of arsenic exposure and neurotoxicity have also been discussed.

show abstract

Section: Molecular Basis Of Arsenic Toxicity and Its Implication In Ad Pathobiologymentioning

confidence: 99%

Section: Molecular Basis Of Arsenic Toxicity and Its Implication In Ad Pathobiologymentioning

confidence: 99%

Exposure to Environmental Arsenic and Emerging Risk of Alzheimer’s Disease: Perspective Mechanisms, Management Strategy, and Future Directions

Rahman

Hannan

Uddin

et al. 2021

Toxics

View full text Add to dashboard Cite

show abstract

“…Evidence suggests that arsenic plays a vital role in neuroinflammation via activation of microglia through secretion of pro-inflammatory cytokines which could damage cognitive function, intellectual ability, learning and memory functions [13,44]. Arsenic administration augmented ROS-mediated expression of pro-inflammatory cytokines in rats via activation of MAP kinase and protein kinase C through increased mRNA levels of pro-inflammatory markers such as TNFα, IL-1β, and IFNγ with protein expression of TNFα and IFNγ [45].…”

Section: Neuroinflammationmentioning

confidence: 99%

“…Arsenic has shown its mutagenic response via disruption to mitochondrial function. As-induced perturbation to mitochondrial oxidation caused production of excess superoxide anions which when react with nitric oxide generate highly reactive peroxynitrites [44]. Arsenic toxicity affects mitochondrial membrane potential via generating ROS and DNA fragmentation, and ROS overproduction is associated with apoptosis induction by the release of cytochrome c which activates caspase pathway (Figure 4) [51].…”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

Exposure to Environmental Factor Arsenic and Emerging Risk of Alzheimer’s Disease: Perspective Mechanisms, Management Strategy, And Future Directions

Rahman¹,

Hannan²,

Uddin³

et al. 2021

Preprint

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is one of the most prevailing neurodegenerative diseases, characterized by memory dysfunction and the presence of hyperphosphorylated tau and amyloid β (Aβ) aggregate in multiple brain regions, including the hippocampus and cortex. The exact etiology of AD has not yet been confirmed. However, epidemiological reports suggest that populations who were exposed to environmental hazards are more likely to develop AD than those who were not. Arsenic (As) is a naturally occurring environmental risk factor abundant in the Earth’s crust and human exposure to As predominantly occurs through drinking water. Convincing evidence suggests that As causes neurotoxicity and impairs memory and cognition although the hypothesis and molecular mechanism of As-associated pathobiology in AD are not clear yet. However, exposure to As and its metabolites leads to various pathogenic events such as oxidative stress, inflammation, mitochondrial dysfunctions, ER stress, apoptosis, impaired protein homeostasis, and abnormal calcium signaling. Evidence has indicated that As exposure induces alterations that coincide with most of the biochemical, pathological, and clinical developments of AD. Here, we overview existing literature to gain insights into the plausible mechanisms that underlie As-induced neurotoxicity and the subsequent neurological deficits in AD. Prospective strategies for the prevention and management of arsenic exposure and neurotoxicity have also been discussed.

show abstract

“…The mechanisms of As toxicity include generation of reactive oxidative species, DNA damage, neuronal degradation and inhibition of enzymes. [9][10][11] Cadmium (Cd) can be taken up via the lungs, e.g. by smoking, and the gastrointestinal tract (drinking water and food).…”

Section: Toxicity Of Arsenic Cadmium Mercury and Leadmentioning

confidence: 99%

Exposure to Toxic Metals (As, Cd, Hg, Pb) in Two Artisanal and Small-scale Gold Mining (ASGM) Areas in Zimbabwe

Rakete¹,

Moonga²,

Wahl³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: People living and working in ASGM areas are exposed to toxic metals such as arsenic (As), cadmium (Cd), mercury (Hg) and lead (Pb). Whereas Hg is purposely used to extract the gold from the ore, the other toxic metals can be liberated from the ore during the mining process. These metals can contaminate drinking water and food and are thus, a source of exposure for people living in these mining areas. However, there is limited to no data about the exposure to toxic metals of people living in ASGM areas. Therefore, the purpose of this study was to conduct biomonitoring of people identifying themselves as artisanal gold miners. Methods: Blood and urine were collected from 207 people living and working in two ASGM areas in Zimbabwe. Hg in whole blood and urine was analyzed by direct mercury analysis, Pb in blood as well as As and Cd in urine were analyzed by GF-AAS. The results were evaluated by descriptive analysis and correlated with the location, age, fish consumption, years living and working in the area. Results: Median As level in urine was 10.0 µg/l (range from below limit of detection to 460 µg/l). Median Cd level in urine was 0.3 µg/l (range from below limit of detection to 11.4 µg/l). Median Hg levels in blood / urine were 2.7 / 5.2 µg/l (range from 0.2 to 167 µg/l / 0.1 to 612 µg/l). Median Pb level in blood was 19.9 µg/l (range from 6.6 to 276 µg/l). As expected, the Hg levels were frequently above international reference values (e. g. NHANES, blood: 34%, urine: 69%). For Pb and Cd, a considerable number of participants (32% and 22% respectively) were above the reference values (NHANES / National Health and Nutrition Examination Survey) and for As 33% of the participants were above the reference value (UBA/ German Environment Agency). Conclusions: Hg levels were, as expected in ASGM areas, mainly above reference and threshold values. A high proportion of As, Cd and Pb levels were also above reference levels. Therefore, the exposure to toxic metals in the two ASGM areas in Zimbabwe is relevant for public health.

show abstract

Neurotoxic Mechanism of Arsenic: Synergistic Effect of Mitochondrial Instability, Oxidative Stress, and Hormonal-Neurotransmitter Impairment

Cited by 58 publications

References 43 publications

Exposure to Environmental Arsenic and Emerging Risk of Alzheimer’s Disease: Perspective Mechanisms, Management Strategy, and Future Directions

Exposure to Environmental Arsenic and Emerging Risk of Alzheimer’s Disease: Perspective Mechanisms, Management Strategy, and Future Directions

Exposure to Environmental Factor Arsenic and Emerging Risk of Alzheimer’s Disease: Perspective Mechanisms, Management Strategy, And Future Directions

Exposure to Toxic Metals (As, Cd, Hg, Pb) in Two Artisanal and Small-scale Gold Mining (ASGM) Areas in Zimbabwe

Contact Info

Product

Resources

About