Arsenic chelators

One osmium complex of the phosphorus-arsenic chelate As—Pf—As (bis(2-diphenyl-arsinoethyI)phenylphosphine, (Ph2AsCH2CH2)2PPh) has been made from 0s04 and the ligand in HC1 it is the orange Os(As—Pf—As)C13.457... 

Arsine/phosphinepoisoning There is no antidote for Arsine or phosphine poisoning. Do not administer arsenic chelating drugs. Patient may need blood transfusions. 

Karman, G.M., Flora, S.J.S. (2006). Combined administration of N-acetylcysteine (NAC) and monoisoamyl DMSA on tissue oxidative stress during arsenic chelation therapy. Biol. Trace Elem. Res. 110 43-60. 

A chelator should be given if there is dyspnea, pulmonary edema, or skin bums larger than pahn size (Goldfrank et al, 2002). BAL is the traditional arsenic chelator, but it has numerous side effects. The deep intramuscular injections are very painful and BAL can cause hypertension, tachycardia, and vomiting. 2,3-Dimercaptosuccinic acid (DMSA, Succimer ) can also be used to chelate arsenic (Graziano et al, 1978). 2,3-Dimercapto-l-propanesulfonic acid (DMPS) is used in Europe and has been effective in protecting rabbits from the lethal effects of lewisite (Aposhian et al, 1982). 

CHjSH CHSH-CHjOH. Usually obtained as an oil, m.p. 77 C. Developed as an antidote to poisoning by organic arsenicals by external application, it is of use in poisoning by Hg, Cu, Zn, Cd but not Pb. It acts by forming a chelate with the metal and so removing it from the system. 

Oxidation Trivalent arsenic citric acid or EDTA Potassium permanganate depending on chelating agent, metal chelate is either strongly sorbed to soil or is highly mobile and can be flumbed usinj water or dilute acid solutions. Oxidizes trivalent arsenic to pentavalent... 

Alkaline phosphatases [AP, orthophosphoric-monoester phosphorylase (alkaline optimum) EC 3.1.3.1] represent a large family of almost ubiquitous isoenzymes found in organisms from bacteria to animals. In mammals, there are two forms of AP, one form present in a variety of tissues and another form found only in the intestines. They share common attributes in that the phosphatase activity is optimal at pH 8-10, is activated by the presence of divalent cations, and is inhibited by cysteine, cyanides, arsenate, various metal chelators, and phosphate ions. Most conjugates created with AP utilize the form isolated from calf intestine. 

BAL is the standard treatment for poisoning by arsenic compounds and will alleviate some effects from exposure to arsenic vesicants. It may also decrease the severity of skin and eye lesions if applied topically within minutes after decontamination is complete (i.e., within 2-5 minutes postexposure). Additional chelating agents for the treatment of systemic arsenic toxicity include meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-l-propanesulfonic acid (DMPS). 

Arsenic uptake in rabbit intestine is inhibited by phosphate, casein, and various metal-chelating agents (USEPA 1980). Mice and rabbits are significantly protected against sodium arsenite intoxication by (V-(2,3-dimercaptopropyl)phthalamidic acid (Stine et al. 1984). Conversely, the toxic effects of arsenite are potentiated by excess dithiols, cadmium, and lead, as evidenced by reduced food efficiency and disrupted blood chemistry in rodents (Pershagen and Vahter 1979). 

Matsunaga, H., Yokoyama, T., Eldridge, R.J., Bolto, B.A. 1996. Adsorption characteristics of arsenic(lll) and arsenic(V) on iron(lll)-loaded chelating resin having lysine-Na,Na-diacetic acid moiety. Reactive and Functional Polymers, 29, 167-174. 

Chanda, M., O Driscoll, K. F., Rempel, G. L., Ligand exchange sorption of arsenate and arsenite anions by chelating resins in ferric ion form I. Weak-base chieating resin Dow XFS-4195. Reactive Polym. 7,1988, 251-261. 

On the other hand, several ROS are highly cytotoxic. Consequently, eukaryotic cells have developed an elaborate arsenal of antioxidant mechanisms to neutrahze their deleterious effects (enzymes such as superoxide dismutases, catalases, glutathione peroxidases, thioredoxin inhibitors of free-radical chain reaction such as tocopherol, carotenoids, ascorbic acid chelating proteins such as lactoferrin and transferrin). It can be postulated that ROS may induce an oxidative stress leading to cell death when the level of intracellular ROS exceeds an undefined threshold. Indeed, numerous observations have shown that ROS are mediators of cell death, particularly apoptosis (Maziere et al., 2000 Girotti, 1998 Kinscherf et al., 1998 Suzuki et al., 1997 Buttke and Sanstrom, 1994 Albina et al., 1993). 

Dimercaprol (BAL, British Anti-Lewisite) was developed in World War 11 as an antidote against vesicant organic arsenicals (B). It is able to chelate various metal ions. Dimercaprol forms a liquid, rapidly decomposing substance that is given intramuscularly in an oily vehicle. A related compound, both in terms of structure and activity, is di-mercaptopropanesulfonic acid, whose sodium salt is suitable for oral administration. Shivering, fever, and skin reactions are potential adverse effects. 

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