Environmental arsenic exposure and its contribution to human diseases, toxicity mechanism and management.

Arsenic (As) contamination affects hundreds of millions of people globally. Although the number of patients with chronic As exposure is large, the symptoms and long-term clinical courses of the patients remain unclear. In addition to reviewing the literature on As contamination and toxicity, we provide useful clinical information on medical care for As-exposed patients. Further, As metabolite pathways, toxicity, speculated toxicity mechanisms, and clinical neurological symptoms are documented. Several mechanisms that seem to play key roles in As-induced neurotoxicity, including oxidative stress, apoptosis, thiamine deficiency, and decreased acetyl cholinesterase activity, are described. The observed neurotoxicity predominantly affects peripheral nerves in sensory fibers, with a lesser effect on motor fibers. A sural nerve biopsy showed the axonal degeneration of peripheral nerves mainly in small myelinated and unmyelinated fibers. Exposure to high concentrations of As causes severe central nervous system impairment in infants, but no or minimal impairment in adults. The exposure dose–response relationship was observed in various organs including neurological systems. The symptoms caused by heavy metal pollution (including As) are often nonspecific. Therefore, in order to recognize patients experiencing health problems caused by As, a multifaceted approach is needed, including not only clinicians, but also specialists from multiple fields.

https://www.mdpi.com/1422-0067/20/14/3418/pdf

Arsenic Neurotoxicity in Humans

Arsenic is a metalloid found in groundwater as a byproduct of soil/rock erosion and industrial and agricultural processes. This xenobiotic elicits its toxicity through different mechanisms, and it has been identified as a toxicant that affects virtually every organ or tissue in the body. In the central nervous system, exposure to arsenic can induce cognitive dysfunction. Furthermore, iAs has been linked to several neurological disorders, including neurodevelopmental alterations, and is considered a risk factor for neurodegenerative disorders. However, the exact mechanisms involved are still unclear. In this review, we aim to appraise the neurotoxic effects of arsenic and the molecular mechanisms involved. First, we discuss the epidemiological studies reporting on the effects of arsenic in intellectual and cognitive function during development as well as studies showing the correlation between arsenic exposure and altered cognition and mental health in adults. The neurotoxic effects of arsenic and the potential mechanisms associated with neurodegeneration are also reviewed including data from experimental models supporting epidemiological evidence of arsenic as a neurotoxicant. Next, we focused on recent literature regarding arsenic metabolism and the molecular mechanisms that begin to explain how arsenic damages the central nervous system including, oxidative stress, energy failure and mitochondrial dysfunction, epigenetics, alterations in neurotransmitter homeostasis and synaptic transmission, cell death pathways, and inflammation. Outlining the specific mechanisms by which arsenic alters the cell function is key to understand the neurotoxic effects that convey cognitive dysfunction, neurodevelopmental alterations, and neurodegenerative disorders.

Arsenic-induced neurotoxicity: a mechanistic appraisal.

Continuous globalization and industrialization have ensured metals are an increasing aspect of daily life. Their usefulness in manufacturing has made them vital to national commerce, security and global economy. However, excess exposure to metals, particularly as a result of environmental contamination or occupational exposures, has been detrimental to overall health. Excess exposure to several metals is considered environmental risk in the aetiology of several neurological and neurodegenerative diseases. Metal-induced neurotoxicity has been a major health concern globally with intensive research to unravel the mechanisms associated with it. Recently, greater focus has been directed at epigenetics to better characterize the underlying mechanisms of metal-induced neurotoxicity. Epigenetic changes are those modifications on the DNA that can turn genes on or off without altering the DNA sequence. This review discusses how epigenetic changes such as DNA methylation, post translational histone modification and noncoding RNA-mediated gene silencing mediate the neurotoxic effects of several metals, focusing on manganese, arsenic, nickel, cadmium, lead, and mercury.

Epigenetic influence of environmentally neurotoxic metals.

Arsenic (As) toxicity has become a public health and environmental problem, which is a serious issue in certain parts of the world. Many people are exposed to As through contaminated drinking water, food and soil, through occupation, etc. Chronic As exposure is linked to various hostile health effects including skin problems, cancer, diabetes, cardiovascular disease, reproductive and developmental and neurological problems in exposed subjects. Experimental existing data indicate that chronic As exposure affects the nervous system by impairing the nerve and brain tissues of the exposed animals, and clinical studies indicate that As exposure leads to both central nervous system and peripheral nervous system impairments and also causes depression, memory impairment and difficulty in problem solving, affects body coordination, etc. Various prenatal and postnatal studies with respect to As exposure also suggest that developing offspring and young children are susceptible to As exposure. The only solution to this serious health problem is to stop occupational As exposure and provide As free drinking water to the affected population.

Arsenic exposure with reference to neurological impairment: an overview.

More than 140 million people drink arsenic-contaminated groundwater. It is unknown how much arsenic exposure is necessary to cause neurological impairment. Here, we evaluate the relationship between neurological impairments and the arsenic concentration in drinking water (ACDW). A cross-sectional study design was employed. We performed medical examinations of 1867 residents in seven villages in the Thabaung township in Myanmar. Medical examinations consisted of interviews regarding subjective neurological symptoms and objective neurological examinations of sensory disturbances. For subjective neurological symptoms, we ascertained the presence or absence of defects in smell, vision, taste, and hearing; the feeling of weakness; and chronic numbness or pain. For objective sensory disturbances, we examined defects in pain sensation, vibration sensation, and two-point discrimination. We analyzed the relationship between the subjective symptoms, objective sensory disturbances, and ACDW. Residents with ACDW ≥ 10 parts per billion (ppb) had experienced a “feeling of weakness” and “chronic numbness or pain” significantly more often than those with ACDW  50 ppb). These data suggest a threshold for the occurrence of peripheral neuropathy due to arsenic exposure, and indicate that the arsenic concentration in drinking water should be less than 10 ppb to ensure human health.

/pdf/peripheral-neuropathy-induced-by-drinking-water-contaminated-4lyqy4k4ru.pdf

Peripheral neuropathy induced by drinking water contaminated with low-dose arsenic in Myanmar

Movement disorders in Indochina: Resource challenges and future solutions

The aim of the study was to study the profile of Guillain‐Barré syndrome (GBS) patients admitted at Yangon General Hospital (YGH), Myanmar.

Win Min Thit

Papers

Peripheral neuropathy induced by drinking water contaminated with low-dose arsenic in Myanmar

Movement disorders in Indochina: Resource challenges and future solutions

Guillain‐Barré syndrome (GBS) in a tertiary general hospital at Yangon, Myanmar