Mechanistic understanding of the toxic effects of arsenic and warfare arsenicals on human health and environment

Abstract

Worldwide, more than 200 million people are estimated to be exposed to unsafe levels of arsenic. Chronic exposure to unsafe levels of groundwater arsenic is responsible for multiple human disorders, including dermal, cardiovascular, neurological, pulmonary, renal, and metabolic conditions. Consumption of rice and seafood (where high levels of arsenic are accumulated) is also responsible for human exposure to arsenic. The toxicity of arsenic compounds varies greatly and may depend on their chemical form, solubility, and concentration. Surprisingly, synthetic organoarsenicals are extremely toxic molecules which created interest in their development as chemical warfare agents (CWAs) during World War I (WWI). Among these CWAs, adamsite, Clark I, Clark II, and lewisite are of critical importance, as stockpiles of these agents still exist worldwide. In addition, unused WWII weaponized arsenicals discarded in water bodies or buried in many parts of the world continue to pose a serious threat to the environment and human health. Metabolic inhibition, oxidative stress, genotoxicity, and epigenetic alterations including micro-RNA-dependent regulation are some of the underlying mechanisms of arsenic toxicity. Mechanistic understanding of the toxicity of organoarsenicals is also critical for the development of effective therapeutic interventions. This review provides comprehensive details and a critical assessment of recently published data on various chemical forms of arsenic, their exposure, and implications on human and environmental health. Graphical abstract

Heavy Metals, Halogenated Hydrocarbons, Phthalates, Glyphosate, Cordycepin, Alcohol, Drugs, and Herbs, Assessed for Liver Injury and Mechanistic Steps

“…Arsenic is frequently found in the environment [36,44,45] including the atmosphere originating from natural sources such as volcanic eruptions and industrial processes [44]. This heavy metal is also a contaminant of soils [45], surface water [45] and ground water used as drinking water [44,46,47], and food [44,46].…”

“…Arsenic is frequently found in the environment [36,44,45] including the atmosphere originating from natural sources such as volcanic eruptions and industrial processes [44]. This heavy metal is also a contaminant of soils [45], surface water [45] and ground water used as drinking water [44,46,47], and food [44,46]. In addition, arsenic was used in chemical warfare agents [44,45] and is a known component of some conventional or traditional medicines [36,44,45,[48][49][50][51].…”

“…This heavy metal is also a contaminant of soils [45], surface water [45] and ground water used as drinking water [44,46,47], and food [44,46]. In addition, arsenic was used in chemical warfare agents [44,45] and is a known component of some conventional or traditional medicines [36,44,45,[48][49][50][51].…”

“…Prolonged and acute ingestion of arsenic leads to toxicity of many organs including the liver [44][45][46][47], associated with clinical features of arsenic poisoning [44][45][46]49,51]. Increased LTs such as ALT, AST or ALP have variably been published [49,50,[52][53][54] with significantly higher values in patients with high arsenic exposure [53].…”

Arsenic Soil Contamination and Its Effects on 5-Methylcytosine Levels in Onions and Arsenic Distribution and Speciation

“…Arsenic pollution is serious and global environmental problem. More than 200 million people worldwide are affected by high arsenic toxicity and large areas of contaminated soil [ 1 , 2 , 3 ]. Arsenic is a toxic metalloid with carcinogenic and mutagenic effects and has strong, negative effects on the Human Development Index, public health, and life expectancy [ 4 , 5 , 6 , 7 ].…”