Thus, by a variety of mechanisms arsenate leads to an impairment of cell respiration and subsequently diminished ATP formation. This is consistent with observed ATP depletion of exposed cells and histopathological findings of mitochondrial and cell swelling, glycogen depletion in liver cells and fatty change in liver, heart and kidney. Experiments demonstrated enhanced arterial thrombosis in a rat animal model, elevations of serotonin levels, thromboxane A[2] and adhesion proteins in platelets, while human platelets showed similar responses. The effect on vascular endothelium may eventually be mediated by the arsenic-induced formation of nitric oxide. It was demonstrated that +3 As concentrations substantially lower than concentrations required for inhibition of the lysosomal protease cathepsin L in B cell line TA3 were sufficient to trigger apoptosis in the same B cell line, while the latter could be a mechanism mediating immunosuppressive effects. Kinetics
The two forms of inorganic arsenic, reduced (trivalent As(III)) and oxidized (pentavalent As(V)), can be absorbed, and accumulated in tissues and body fluids. In the liver, the metabolism of arsenic involves enzymatic and non-enzymatic methylation; the most frequently excreted metabolite (≥ 90%) in the urine of mammals is dimethylarsinic acid or cacodylic acid, DMA(V). Dimethylarsenic acid is also known as Agent Blue and was used as herbicide in the American war in Vietnam. In humans inorganic arsenic is reduced nonenzymatically from pentoxide to trioxide, using glutathione or it is mediated by enzymes. Reduction of arsenic pentoxide to arsenic trioxide increases its toxicity and bio availability, Methylation occurs through methyltransferase enzymes. S-adenosylmethionine (SAM) may serve as methyl donor.
This presents a potentially significant public health concern in some areas of the United States (e.g., New Jersey, Washington, and Wisconsin), where large areas of land used historically as orchards have been converted into residential developments.Some modern uses of arsenic-based pesticides still exist. Chromated copper arsenate has been registered for use in the United States since the 1940s as a wood preservative, protecting wood from insects and microbial agents. In 2003, manufacturers of chromated copper arsenate instituted a voluntary recall of residential uses of wood treated with the chemical. The Environmental Protection Agency Act2008 final report stated that chromated copper arsenate is still approved for use in nonresidential applications, such as in marine facilities (pilings and structures), utility poles, and sand highway structures. Copper smelting
Exposure studies in the copper smelting industry are much more extensive and have established definitive links between arsenic, a by-product of copper smelting, and lung cancer via inhalation. Dermal and neurological effects were also increased in some of these studies. Although as time went on, occupational controls became more stringent and workers were exposed to reduced arsenic concentrations, the arsenic exposures measured from these studies ranged from about 0.05 to 0.3 mg/m3 and are significantly higher than airborne environmental exposures to arsenic (which range from 0 to 0.000003 mg/m3). Pathophysiology
Arsenic interferes with cellular longevity by allosteric inhibition of an essential metabolic enzyme pyruvate dehydrogenase complex, which catalyzes the oxidation of pyruvate to acetyl-CoA by NAD+. With the enzyme inhibited, the energy system of the cell is disrupted resulting in cellular apoptosis.