Metabolism and disposition of inorganic arsenic in laboratory animals and humans

Abstract

The carcinogenicity of inorganic arsenic in humans, particularly in the lung and skin, has been reasonably well established through epidemiological investigations. However, there is no substantial experimental evidence for carcinogenicity in animals to support the human studies. Studies of metabolism and disposition of inorganic arsenic in various animal species are particularly relevant to determining the factors that might account for the lack of an animal model. Numerous studies of this type have been reported, but there do not appear to be clear qualitative or quantitative differences in the overall fate and disposition of inorganic arsenic in most animalsversus humans, although little is known at the cellular and subcellular level.Sulphur chemistry, especially thiol status, is emerging as an important regulating factor in the overall fate and distribution of inorganic arsenic in the body, playing a role in the initial reduction of arsenate to arsenite and subsequent methylation, and possibly in determining tissue affinity and distribution properties. The metabolism of inorganic arsenic can be viewed as a redox cycle in which thiol compounds such as glutathione (GSH) possibly function as reducing agents and methyl donors as oxidising agents. One explanation for the possible sensitivity of certain malnourished human populations to the carcinogenic effects of inorganic arsenic may be related to the reduced availability of nonprotein sulphhydryl compounds such as GSH needed to drive the redox cycle and facilitate arsenic detoxification. Future carcinogenicity studies of inorganic arsenic in animals could be designed to address directly this aspect of the problem.

Sodium Arsenite Induced Systemic Organ Damage and Changes in Various Blood Parameters in Mice

“…Inorganic arsenic is reported to bind to the α-chain of hemoglobin and thereby accumulates in the RBCs. 20 Recently, we have also observed changes in RBC morphology in SA-exposed mice 4 that might cause destruction of RBC leading to development of anemia. 21 All these findings may support the fact of decreased hemoglobin level obtained in the present study.…”

“…[1][2][3] Ingested inorganic arsenic is readily absorbed through the gastrointestinal tract and distributed in various tissues through blood circulation. 4 This arsenic eventually causes growth retardation, blood cells distortion and elevation of various serum enzymes like lactate dehydrogenase (LDH), alkaline phosphatase (ALP), serum glutamic pyruvic transaminase (SGPT) etc. in human and rodents.…”

Groundwater Arsenic Contamination in West Bengal: Current Scenario, Effects and Probable Ways of Mitigation

“…Recent studies have shown that GSH elevation is a natural reaction to arsenic attack which probably acts as a protective mechanism (McKinney, 1992;Mazumder et al, 1988). The situation becomes more critical when the availability of free thiol group is low (malnutrition/protein deficiency) and enhanced expression of toxicity can occur.…”

Effects of protein deficient diets on the developmental toxicity of inorganic arsenic in mice

“…Arsenic is then methylated to methylarsonic acid (MMA) and dimethylarsinic acid (DMA) (McKinney, 1992), and Sadenosylmethionine (SAM) has been shown to be the primary methyl donor in the arsenic transmethylation reactions (Vahter, 2002).…”