Arsenic: toxicity, oxidative stress and human disease

Abstract

Arsenic (As) is a toxic metalloid element that is present in air, water and soil. Inorganic arsenic tends to be more toxic than organic arsenic. Examples of methylated organic arsenicals include monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)]. Reactive oxygen species (ROS)-mediated oxidative damage is a common denominator in arsenic pathogenesis. In addition, arsenic induces morphological changes in the integrity of mitochondria. Cascade mechanisms of free radical formation derived from the superoxide radical, combined with glutathione-depleting agents, increase the sensitivity of cells to arsenic toxicity. When both humans and animals are exposed to arsenic, they experience an increased formation of ROS/RNS, including peroxyl radicals (ROO•), the superoxide radical, singlet oxygen, hydroxyl radical (OH•) via the Fenton reaction, hydrogen peroxide, the dimethylarsenic radical, the dimethylarsenic peroxyl radical and/or oxidant-induced DNA damage. Arsenic induces the formation of oxidized lipids which in turn generate several bioactive molecules (ROS, peroxides and isoprostanes), of which aldehydes [malondialdehyde (MDA) and 4-hydroxy-nonenal (HNE)] are the major end products. This review discusses aspects of chronic and acute exposures of arsenic in the etiology of cancer, cardiovascular disease (hypertension and atherosclerosis), neurological disorders, gastrointestinal disturbances, liver disease and renal disease, reproductive health effects, dermal changes and other health disorders. The role of antioxidant defence systems against arsenic toxicity is also discussed. Consideration is given to the role of vitamin C (ascorbic acid), vitamin E (α-tocopherol), curcumin, glutathione and antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase in their protective roles against arsenic-induced oxidative stress.

Cardiovascular effects of arsenic: clinical and epidemiological findings

“…They include superoxide anion, hydroxyl radical, hydrogen peroxide, reactive nitrogen species, and As-centered and As peroxyl radicals (Bao and Shi 2010b;Hughes et al 2011;Flora 2011). The mechanisms of ROS formation by As are not completely clear: they may be produced during oxidation of arsenite (III) to arsenate (V) during metabolization, by stimulation of the enzymes NADH or NADPH oxidase (Smith et al 2001), and NOX ), or by mobilization of free iron from ferritin (Shi et al 2004;Flora 2011;Jomova et al 2011). …”

“…Since As is metabolized from the blood within a period of hours, blood As levels -normally < 1 g/l -are not a good indicator of longterm exposure, and they are only partially correlated with As in drinking water. The majority of absorbed As is excreted in the urine, normally within 1-2 days, so that urinary As is considered a reliable marker of recent exposure (Jomova et al 2011). However, as previously mentioned not all forms of As are (equally) toxic, so total urinary As should be considered only a screening test, or suitable for population studies or continuous professional exposure.…”

Role of endoplasmic reticulum stress in drug‐induced toxicity

“…Unsurprisingly, investigations in noncancerous cells and in rodents suggested that some of these side effects could be secondary to oxidative stress and mitochondrial dysfunction (Aposhian and Aposhian 2006; Jomova et al. 2011; Mathews et al. 2013; Garcia‐Sevillano et al.…”

Arsenic translocation in rice cultivation and its implication for human health

“…Arsenic toxicity is based on species (Jomova et al, 2011). The rice grain contains both organic and inorganic As (iAs).…”