Randomized Placebo-Controlled Trial of 2,3-Dimercaptosuccinic Acid in Therapy of Chronic Arsenicosis Due to Drinking Arsenic-Contaminated Subsoil Water

Mazumder, D. N. Guha; Uc, Ghoshal; Saha, Jyoti Prasad; Santra, Amal; De, Binay K; Chatterjee, Amit; Dutta, Souvik; Angle, Carol R.; Centeno, José A.

doi:10.3109/15563659809162616

Cited by 85 publications

(43 citation statements)

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“…The arsenic issue is perhaps the most distinct in Bangladesh and West Bengal, as millions of handpumped tube wells yield drinking water with arsenic concentrations above 10 μg L -1 , which is the World Health Organization drinking water guideline (18)(19)(20). In West Bengal, India, arsenic concentrations in some tube wells go as high as 3400 μg L -1 (21). This study has investigated the effects of arsenic on biochemical parameters indicative of changes in haeme biosynthesis, liver and kidney oxidative stress, and liver damage, and has investigated the ability of …”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Selenium, Calcium, and Magnesium Against Arsenic-Induced Oxidative Stress in Male Rats

Srivastava

Subramanian

Madamwar

et al. 2010

Archives of Industrial Hygiene and Toxicology

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Inorganic arsenic is a potent carcinogen and environmental pollutant. More than one hundred million people are reported to be exposed to elevated concentrations of arsenic mainly via drinking water. Essential trace elements can affect toxicity of metals by interacting with metals at the primary site of action and can also modify the body's response to toxic metals by altering their metabolism and transport. This study investigates the effects of concomitant administration of selenium, magnesium, and calcium with arsenic on blood biochemistry and oxidative stress. Selenium was the most effective in reducing arsenic-induced inhibition of blood δ-aminolevulinic acid dehydratase (ALAD) activity and liver oxidative stress. Calcium and magnesium also showed favourable effects on haematological and other biochemical parameters. Because selenium was the most effective, it should be added to chelation therapy to achieve the best protective effects against arsenic poisoning in humans.

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Section: Discussionmentioning

confidence: 99%

Protective Effects of Selenium, Calcium, and Magnesium Against Arsenic-Induced Oxidative Stress in Male Rats

Srivastava

Subramanian

Madamwar

et al. 2010

Archives of Industrial Hygiene and Toxicology

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“…The therapeutic effect of the dithiols is attributed to the ability of their vicinal thiol groups to react with trivalent arsenicals forming a saturated five-member heterocyclic ring [25,26]. However, a double-blind, randomized controlled trial study conducted on few selected patients from arsenic-affected West Bengal (India) regions with oral administration of DMSA suggested that DMSA was not effective in producing any clinical or biochemical benefits or any histopathological improvements of skin lesions [27]. Although DMSA is an effective drug for the treatment of metal intoxication, however, because of its hydrophilic and lipophobic properties, it is unable to pass through cell membranes [28,29].…”

Section: Introductionmentioning

confidence: 99%

Quercetin Administration During Chelation Therapy Protects Arsenic-Induced Oxidative Stress in Mice

Mishra

Flora

2008

Biol Trace Elem Res

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We studied the efficacy of quercetin and a thiol chelating agent, monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA) either individually or in combination against arsenic-induced oxidative stress and mobilization of metal in mouse. Animals were chronically exposed to 25 ppm arsenite as sodium arsenite in drinking water for 12 months followed by treatment with MiADMSA (0.2 mmol/kg, orally), quercetin (0.2 mmol, orally) either alone or in combination, once daily for 5 consecutive days. Arsenic exposure led to a significant depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity, glutathione, white (WBC) and red blood cell (RBC) counts, and an increase in platelet levels while significantly increasing the level of reactive oxygen species (in RBCs). Hepatic reduced catalase (CAT) and glutathione peroxidase activities showed a depletion, whereas thiobarbituric acid reactive substances (TBARS) levels increased on arsenic exposure indicating arsenite-induced oxidative stress in blood and liver. Kidney CAT activity showed a depletion, whereas TBARS levels increased on arsenic exposure. These biochemical changes were accompanied by an increase in blood, liver, and kidney arsenic concentration. Treatment with MiADMSA was effective in increasing ALAD activity, whereas quercetin was ineffective when given alone. Quercetin when co-administered with MiADMSA also provided no additional beneficial effect on blood ALAD activity but significantly brought altered platelet counts nearer to the normal value. In contrast, administration of quercetin alone provided significant beneficial effects on hepatic oxidative stress and kidney TBARS levels. Renal biochemical variables remained insensitive to arsenic and any of the treatments. Interestingly, combined administration of quercetin with MiADMSA had a remarkable effect in depleting total arsenic concentration from blood and soft tissues. These results lead us to conclude that quercetin administration during chelation treatment had some beneficial effects particularly on the protection of inhibited blood ALAD activity and depletion of arsenic level from target organs. The study supports our earlier conclusion that a co-administration of an antioxidant particularly flavonoids more beneficial than monotherapy with the chelating agents to achieve optimal effects of chelation in arsenite toxicity.

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“…A quantitative evaluation of three drugs reveals that DMPS is 28 times more effective than BAL in arsenic therapy in mice, and DMSA and DMPS are equally effective. Guha Majumder et al evaluated the efficacy of DMPS in a single blind placebo control trial of patients suffering from chronic arsenic poisoning in West Bengal, India 53) . DMPS was given in a 100 mg capsule dose 4 times a day for 7 d for four courses with a one-week drug free period between courses.…”

Section: Conventional Chelating Agents and Their Drawbacksmentioning

confidence: 99%

Strategies for Safe and Effective Therapeutic Measures for Chronic Arsenic and Lead Poisoning

Kalia¹,

Flora²

2005

Journal of Occupational Health

267

161

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Strategies for Safe and Effective Therapeutic Measures for Arsenic and LeadPoisoning: Kiran Kalia, et al. Department of Biosciences, Sardar Patel University, IndiaExposure to toxic metals remains a widespread occupational and environmental problem in world. There have been a number of reports in the recent past suggesting an incidence of childhood lead poisoning and chronic arsenic poisoning due to contaminated drinking water in many areas of West Bengal in India and Bangladesh has become a national calamity. Low level metal exposure in humans is caused by air, food and water intake. Lead and arsenic generally interferes with a number of body functions such as the central nervous system (CNS), the haematopoietic system, liver and kidneys. Over the past few decades there has been growing awareness and concern that the toxic biochemical and functional effects are occurring at a lower level of metal exposure than those that produce overt clinical and pathological signs and symptoms. Despite many years of research, we are still far from an effective treatment of chronic plumbism and arsenicosis. Medical treatment of acute and chronic lead and arsenic toxicity is furnished by chelating agents. Chelating agents are organic compounds capable of linking together metal ions to form complex ring-like structures called chelates. They have been used clinically as antidotes for acute and chronic poisoning. 2, 3-dimercaprol (BAL) has long been the mainstay of chelation therapy for lead or arsenic poisoning. Meso 2, 3, -dimercaptosuccinic acid (DMSA) has been tried successfully in animals as well as in a few cases of human lead and arsenic poisoning. DMSA could be a safe and effective method for treating lead or arsenic poisoning, but one of the major disadvantages of chelation with DMSA has been its Review inability to remove lead from the intracellular sites because of its lipophobic nature. Further, it does not provide protection in terms of clinical/ biochemical recovery. A new trend in chelation therapy is to use combined treatment. This includes the use of structurally different chelators or a combination of an adjuvant and a chelator to provide better clinical/ biochemical recovery in addition to lead mobilization. The present review article attempts to provide update information about the current strategies being adopted for a safe, effective and specific treatment for two major toxic metals or metalloid.

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Randomized Placebo-Controlled Trial of 2,3-Dimercaptosuccinic Acid in Therapy of Chronic Arsenicosis Due to Drinking Arsenic-Contaminated Subsoil Water

Abstract: Under the conditions of this study, 2,3-dimercaptosuccinic acid was not effective in producing any clinical or biochemical benefit or any histopathological improvement of skin lesions in patients with chronic arsenicosis.

Cited by 85 publications

References 16 publications

Protective Effects of Selenium, Calcium, and Magnesium Against Arsenic-Induced Oxidative Stress in Male Rats

Protective Effects of Selenium, Calcium, and Magnesium Against Arsenic-Induced Oxidative Stress in Male Rats

Quercetin Administration During Chelation Therapy Protects Arsenic-Induced Oxidative Stress in Mice

Strategies for Safe and Effective Therapeutic Measures for Chronic Arsenic and Lead Poisoning

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