Biotransformation of inorganic arsenic

It has also been shown that arsenic is incorporated into marine and freshwater organisms in the form of both water-soluble and lipid-soluble compounds. Recent studies have shown the presence of arsenite [As(III)], arsenate [As(V)], methylarsonic acid, dimethylarsinic acid and arsenobetaine (AB). Methylated arsenicals also appear in the urine and plasma of mammals, including man, by biotransformation of inorganic arsenic compounds. Several methods have been devised to characterize these arsenicals. 

Vahter M (2000) Genetic polymorphism in the biotransformation of inorganic arsenic and its role in toxicity. Toxicol Lett 112/113 209 - 217. 

Biotransformation of inorganic arsenic in the human body occurs mainly in the liver (but also in other organs), and is considered to be a detoxifying reaction. It occurs by a two-electron reduction of As to As ", followed by oxidative addition of a methyl group to As ". Glutathione and possibly... 

Biotransformation of Inorganic Arsenic Compounds by Freshwater Algae... 

Stolz, J.F., Perera, E., Kilonzo, B., Kail, B., Crable, B., Fisher, E., Ranganathan, M., Wormer, L., Basu, P. (2007). Biotransformation of 3-nitro-4-hydroxybenzene arsonic acid (roxarsone) and release of inorganic arsenic by Clostridium species. Environ. Sci. Technol. 41 818-23. 

Peraza et al. (2003) studied toxicity and metabolism of inorganic arsenic in kidney at low level subcytotoxic concentrations. Human renal proximal tubule epithelial cells (HK-2) were used as model in their study. The authors found that HK-2 cells were capable of biotransforming inorganic arsenic compounds in a pathway involving reduction of arsenate to arsenite. 

Inorganic forms arsenic are more acutely toxic than the organic arsenicals and the toxicity depends upon the oxidation state of arsenic. Conversion between the oxidation states of inorganic arsenic have been shown to occur both in the environment and in the animal body. Recent studies (Vahter and Norin, 1980 Vahter, 1981) have suggested that the differences between the toxicities of trivalent and pentavalent arsenic depend upon the extent of vivo biotransformation to methylated metabolites. Environmental oxidation favors the conversion of trivalent arsenic to pentavalent arsenic. Pentavalent arsenic may be partially reduced vivo to trivalent arse-noxide (R As 0), but it is the vivo reduction of arsenate to arsenite which accounts for both toxicity and antimicrobial actions (Harvey, 1975). Rumen microflora obtained from Holstein cows reduced arsenate to arsenite (Forsberg, 1978). Ginsberg (1965) demon-... 

Vahter, M. (1981) Biotransformation of trivalent and pentavalent inorganic arsenic in mice and rats. Environmental Research, 25(2), 286-93. 

Dimercaprol is FDA-approved as single-agent treatment of acute poisoning by arsenic and inorganic mercury and for the treatment of severe lead poisoning when used in conjunction with edetate calcium disodium (EDTA see below). Although studies of its metabolism in humans are limited, intramuscularly administered dimercaprol appears to be readily absorbed, metabolized, and excreted by the kidney within 4-8 hours. Animal models indicate that it may also undergo biliary excretion, but the role of this excretory route in humans and other details of its biotransformation are uncertain. 

Arsenic toxicity from drinking water is a major public health concern in many countries throughout the world. If exposure is to the inorganic form, the kidneys are the target organ due to its involvement in in vivo biotransformation and elimination. Very few clinical cases of toxicity are reported in humans. Most clinical cases of toxicosis are reported in animals, especially cattle and dogs, by... 

Toxicity of the various arsenic compounds in mammals extends over a wide range, determined in part by unique biochemical actions of each compound, but also by absorbability and efficiency of biotransformation and disposition. Overall, arsines present the greatest toxic hazard, followed closely by arsenites (inorganic trivalent compounds). Inorganic pentavalent compounds are somewhat less toxic that arsenites, while the organic (methylated)... 

---