2.3- Dimercaptopropanol , effect

Coumarin, the lactone of o-hydroxycinnamic acid, and some of its derivatives have been isolated from many plant species 31). Thimann and Bonner 141) attributed the growth-inhibiting effects of coumarin to its action on enzyme sulfhydryl groups. Inhibitory effects of coumarin on Avena coleoptiles and pea stem sections could be overcome by 2,3-dimercaptopropanol (BAL). Coumarin has also been reported to disrupt mitosis 29,30). 

However, dimercaptopropanol is not ideal for chelation therapy. It is unstable in aqueous solution and is easily oxidised so has to be injected intramuscularly as a solution in vegetable oil. This ensures its slow release into body tissues, making for more effective action, but it has a most objectionable odour. The injections are painful and frequently give rise to unpleasant local reactions. 

Because of the ease with which dimercaptopropanol can be broken down in the body there is a danger that chelation, followed by breakdown, will simply result in the translocation of the metal ions to other tissues such as brain or liver. High doses of dimercaptopropanol can adversely affect a number of essential metal-activated enzymes, such as catalase, carbonic anhydrase and peroxidase, and also produce dangerous systemic effects. Dimercaptopropanol cannot be used to remove cadmium because its cadmium complex is toxic to kidney tissue54). 

Lead is widely destributed in the environment, especially in industrial and urban areas, and it is readily absorbed into the mammalian body where it exerts a number of undesirable physiological effects. Its most dramatic action is the inhibition of human red cell 5-aminolaevulinic acid dehydrase activity71), but it also depresses the activities of many enzymes having functionsl -SH groups. Attempts to remove lead from the body using agents such as dimercaptopropanol can result in the formation of lipid-soluble lead complexes that may be carried to the brain and exacerbate the effects of lead poisoning. 

Copper toxicity has been observed, althongh it is not a function of dietary overload. Abnormally low levels of ceruloplasmin associated with the genetic disorder, Wilson s disease, lead to excessive deposition of copper in the central nervous system, ocular tissue, liver, and other organs. Severe psychotic symptoms are observed. Urinary excretion of the copper can be achieved with specific chelating agents such as British anti-lewisite (BAL, 2,3-dimercaptopropanol) or penicillamine, orally administered. Symptoms of the disease are reversed as the copper levels return to normal. Reduction of dietary copper nptake by competition with relatively high levels of oral zinc is also effective. ... 

Similar to the mustard agents, exposure prevention is the first line of defense against lewisite. Rapid decontamination is especially relevant to lewisite exposure due to the rapid development of pain (1-2 min) associated with lewisite exposure. Unlike other vesicants, an effective antidote for lewisite toxicity exists in the form of British anti-lewisite (BAL 2,3-dimercaptopropanol) which binds with arsenicals, thereby countering the lewisite-induced damage. Such chelation therapy is associated with notable side effects (e.g. renal effects) and requires carefiil medical management. More effective analogs of BAL have been developed with less significant side effects. 

Organoarsenicals were used as poison gases in World War I. The most notorious of these was Lewisite (140). During the years before World War II, researchers looked for antidotes and found the compound 2,3-dimercaptopropanol, now commonly known as British Anti-Lewisite or BAL (190). This compound has proven extremely effective in the treatment of lead and mercury poisoning. 

The mechanism of this eflFect is not known. Hill and Starcher (49) postulated that reduction of copper from its divalent (cupric) state to its monovalent (cuprous) state accounted for the impaired absorption of copper in the presence of ascorbic acid they produced the same effect with another reducing agent, dimercaptopropanol (BAL). This explanation has been accepted by others (56), although the oxidation state of copper for maximum intestinal absorption has not been established. An intramucosal competition of ascorbic acid for sulfhydryl sites on metallo-thioneins was demonstrated (57). If this ligand has any regulatory role in copper uptake, this alternative mechanism of ascorbic acid-copper interaction could explain the mechanism. Experimental confirmation of an ascorbic-acid-induced inhibition of copper absorption in the human intestine has not been presented. 

Syrup of ipecac (purging solution) and gastric lavage should be administered within 4-6 h of oral exposure to arsenic. Antidotes include 3-5 mg kg BAL (2,3-dimercaptopropanol) administered intramuscularly. Penicilamine has also been administered with optical neuritis as a side effect. Certain synthetic, water-soluble dimercapto compounds (DMSA - meso-2, 3-dimercaptosuccinic acid and 2,3-dimercaptopro-pane-l-sulfonate) have been found effective. 

For acute toxicity, emesis is recommended. Treatment is symptomatic. A combination of BAL (British AntiLewisite 2,3-dimercaptopropanol) and calcium-ethylene diamine tetraacetic acid has been used successfully in a poisoned infant. Penicillamine has also been used. Recently, oral administration of 2,3-dime-rcaptol-propane sulfonate was found to be effective in experimental rodents. Electrolyte balance must be maintained when gastric lavage is indicated. Potassium ferrocyanide should be added to precipitate the copper. 

Dimercaptopropanol (dmp. Figure 1, also called British Anti-Lewisite) is thought to be useful for the treatment of toxic side effects arising from gold therapy (29). We report here studies on reactions of dmp with red cells treated with EtaPAuCl or auranofin. 

SH SH 2,3-Dimercaptopropanol (BAL) Rat studies suggest BAL is more effective than CaNa2EDTA at chelating lead from bone and soft tissue Delivered as intramuscular injection (can be very painful) May cause reaction in children allergic to peanuts Side effects include fever, nausea, watery eyes, sweating, and unpleasant breath Recommended in conjunction with CaNa2EDTA for BEEs > 70 rg dE- ... 

The toxic effects of arsenic can be counteracted with (1) saline purgatives, (2) various demulcents that coat irritated gastrointestinal mucous membranes, (3) sodium thiosulfate, and (4) mono- and dithiol-containing compounds and 2,3-dimercaptopropanol. Arsenic uptake in rabbit intestine is inhibited by phosphate, casein, and various metal-chelating agents. Mice and rabbits are significantly protected against sodium arsenite intoxication by A-(2,3-dimercaptopropyl)phthalamidic acid. 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. 

Inhibitory effect on intestinal vitamin K synthesis, VI, 41 7,12-DiketochoIanic acid, configuration, VIII, 261 Dimenformon, see Estradiol benzoate 2,3-Dimercaptopropanol (BAL), as antidote against lewisite, VII, 106 mercury, VII, 106 mustard gas, VII, 106... 

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