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      Arsenic toxicity: sources, pathophysiology and mechanism

      , , ,
      Toxicology Research
      Oxford University Press (OUP)

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          Abstract

          Background

          Arsenic is a naturally occurring element that poses a significant threat to human health due to its widespread presence in the environment, affecting millions worldwide. Sources of arsenic exposure are diverse, stemming from mining activities, manufacturing processes, and natural geological formations. Arsenic manifests in both organic and inorganic forms, with trivalent meta-arsenite (As3+) and pentavalent arsenate (As5+) being the most common inorganic forms. The trivalent state, in particular, holds toxicological significance due to its potent interactions with sulfur-containing proteins.

          Objective

          The primary objective of this review is to consolidate current knowledge on arsenic toxicity, addressing its sources, chemical forms, and the diverse pathways through which it affects human health. It also focuses on the impact of arsenic toxicity on various organs and systems, as well as potential molecular and cellular mechanisms involved in arsenic-induced pathogenesis.

          Methods

          A systematic literature review was conducted, encompassing studies from diverse fields such as environmental science, toxicology, and epidemiology. Key databases like PubMed, Scopus, Google Scholar, and Science Direct were searched using predetermined criteria to select relevant articles, with a focus on recent research and comprehensive reviews to unravel the toxicological manifestations of arsenic, employing various animal models to discern the underlying mechanisms of arsenic toxicity.

          Results

          The review outlines the multifaceted aspects of arsenic toxicity, including its association with chronic diseases such as cancer, cardiovascular disorders, and neurotoxicity. The emphasis is placed on elucidating the role of oxidative stress, genotoxicity, and epigenetic modifications in arsenic-induced cellular damage. Additionally, the impact of arsenic on vulnerable populations and potential interventions are discussed.

          Conclusions

          Arsenic toxicity represents a complex and pervasive public health issue with far-reaching implications. Understanding the diverse pathways through which arsenic exerts its toxic effects is crucial to developing effective mitigation strategies and interventions. Further research is needed to fill gaps in our understanding of arsenic toxicity and to inform public health policies aimed at minimising exposure.

          Arsenic toxicity is a crucial public health problem influencing millions of people around the world. The possible sources of arsenic toxicity includes mining, manufacturing processes and natural geological sources. Arsenic exists in organic as well as in inorganic forms. Trivalent meta-arsenite (As3+) and pentavalent arsenate (As5+) are two most common inorganic forms of arsenic. Trivalent oxidation state is toxicologically more potent due to its potential to interact with sulfur containing proteins. Humans are exposed to arsenic in many ways such as environment and consumption of arsenic containing foods. Drinking of arsenic-contaminated groundwater is an unavoidable source of poisoning, especially in India, Bangladesh, China, and some Central and South American countries. Plenty of research has been carried out on toxicological manifestation of arsenic in different animal models to identify the actual mechanism of aresenic toxicity. Therefore, we have made an effort to summarize the toxicology of arsenic, its pathophysiological impacts on various organs and its molecular mechanism of action.

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          Most cited references140

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          Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends.

          Bladder cancer has become a common cancer globally, with an estimated 430 000 new cases diagnosed in 2012.
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            Is Open Access

            ERK/MAPK signalling pathway and tumorigenesis

            Mitogen-activated protein kinase (MAPK) cascades are key signalling pathways that regulate a wide variety of cellular processes, including proliferation, differentiation, apoptosis and stress responses. The MAPK pathway includes three main kinases, MAPK kinase kinase, MAPK kinase and MAPK, which activate and phosphorylate downstream proteins. The extracellular signal-regulated kinases ERK1 and ERK2 are evolutionarily conserved, ubiquitous serine-threonine kinases that regulate cellular signalling under both normal and pathological conditions. ERK expression is critical for development and their hyperactivation plays a major role in cancer development and progression. The Ras/Raf/MAPK (MEK)/ERK pathway is the most important signalling cascade among all MAPK signal transduction pathways, and plays a crucial role in the survival and development of tumour cells. The present review discusses recent studies on Ras and ERK pathway members. With respect to processes downstream of ERK activation, the role of ERK in tumour proliferation, invasion and metastasis is highlighted, and the role of the ERK/MAPK signalling pathway in tumour extracellular matrix degradation and tumour angiogenesis is emphasised.
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              Oxidative Stress: A Key Modulator in Neurodegenerative Diseases

              Oxidative stress is proposed as a regulatory element in ageing and various neurological disorders. The excess of oxidants causes a reduction of antioxidants, which in turn produce an oxidation–reduction imbalance in organisms. Paucity of the antioxidant system generates oxidative-stress, characterized by elevated levels of reactive species (oxygen, hydroxyl free radical, and so on). Mitochondria play a key role in ATP supply to cells via oxidative phosphorylation, as well as synthesis of essential biological molecules. Various redox reactions catalyzed by enzymes take place in the oxidative phosphorylation process. An inefficient oxidative phosphorylation may generate reactive oxygen species (ROS), leading to mitochondrial dysfunction. Mitochondrial redox metabolism, phospholipid metabolism, and proteolytic pathways are found to be the major and potential source of free radicals. A lower concentration of ROS is essential for normal cellular signaling, whereas the higher concentration and long-time exposure of ROS cause damage to cellular macromolecules such as DNA, lipids and proteins, ultimately resulting in necrosis and apoptotic cell death. Normal and proper functioning of the central nervous system (CNS) is entirely dependent on the chemical integrity of brain. It is well established that the brain consumes a large amount of oxygen and is highly rich in lipid content, becoming prone to oxidative stress. A high consumption of oxygen leads to excessive production of ROS. Apart from this, the neuronal membranes are found to be rich in polyunsaturated fatty acids, which are highly susceptible to ROS. Various neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), among others, can be the result of biochemical alteration (due to oxidative stress) in bimolecular components. There is a need to understand the processes and role of oxidative stress in neurodegenerative diseases. This review is an effort towards improving our understanding of the pivotal role played by OS in neurodegenerative disorders.
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                Author and article information

                Journal
                Toxicology Research
                Oxford University Press (OUP)
                2045-4538
                February 01 2024
                January 01 2024
                December 08 2023
                February 01 2024
                January 01 2024
                December 08 2023
                : 13
                : 1
                Article
                10.1093/toxres/tfad111
                7675e51e-0adf-465f-829d-4d2f81e99acb
                © 2023

                https://academic.oup.com/pages/standard-publication-reuse-rights

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