Individual and Combined Effect of Meso-2,3-Dimercaptosuccinic Acid and Allicin on Blood and Tissue Lead Content in Mice

Abstract

It has been shown that garlic and its main bioactive component, allicin, as natural chelating agents can reduce blood and tissue lead content in animal models. In this study the effect of allicin, alone or combined with meso-2,3-dimercaptosuccinic acid (DMSA), in decreasing lead content of blood and tissues of mice was evaluated. Swiss albino mice were exposed to 1000 ppm of lead in water for 35 days and then placed in various treatment groups including groups administered oral allicin, DMSA, or their combination. The concentrations of lead in blood, kidney, liver, bone and brain were measured using atomic absorption spectrophotometry. Both, allicin and DMSA decreased the blood and tissue lead concentration. There was an additive effect of the combined administration of allicin and DMSA in reducing bone lead. No side effect was observed in all treated groups. Combined use of DMSA and allicin seems to be a better choice in the treatment of chronic lead intoxication.

Key words

lead poisoning - chelating agent - allicin - meso‐2,3‐dimecaptosuccinic acid (DMSA) - garlic - Allium sativa - Liliaceae

References

• 1 Kosnett M J. Lead. Ford MD, Delaney KA, Ling LJ, Erickson T Clinical toxicology. Philadelphia; Saunders 2001
• 2 Gwaltney-Beant S. Lead. Plumlee KH Clinical veterinary toxicology. St. Louis; Mosby 2003
• 3 Radostits O M, Gay C C, Hinchcliff K W, Constable P D. Veterinary medicine, 10th edition. London; Saunders & Elsevier 2007
• 4 Schwarts J, Levin R. The risk of lead toxicity in homes with lead paint hazard.  Environ Res. 1991;  54 1-7
• 5 Patrick L. Lead toxicity, part II: the role of free radical damage and the use of antioxidants in the pathology and treatment of lead toxicity.  Altern Med Rev. 2006;  11 114-126
• 6 Patrick L. Lead toxicity, a review of the literature. Part I: exposure, evaluation and treatment.  Altern Med Rev. 2006;  11 2-22
• 7 Flora S J S, Bhattacharya R, Vijayaraghavan R. Combined therapeutic potential of meso-2, 3-dimercaptosuccinic acid and calcium disodium edentate on the mobilization and distribution of lead in experimental lead intoxication in rats.  Fundam Appl Toxicol. 1995;  25 233-240
• 8 Denver M C, Tell L A, Galey F D, Trupkiewicz J G. Comparison of two heavy metal chelators for treatment of lead toxicosis in cockatiels.  Am J Vet Res. 2000;  61 935-940
• 9 Knight T E, Kent M, Junk J E. Succimer for treatment of lead toxicosis in two cats.  J Am Vet Med Assoc. 2001;  218 1946-1948
• 10 Casteel S W. Lead. Peterson ME, Talcott PA Small animal toxicology, 2nd edition. St. Louis; Saunders-Elsevier 2006
• 11 Kalia K, Flora S J S. Strategies for safe and effective therapeutic measures for chronic arsenic and lead poisoning.  J Occup Health. 2005;  47 1-21
• 12 Najar-Nezhad V, Aslani M R, Balali-Mood M. Evaluation of allicin for the treatment of experimental induced subacute lead poisoning in sheep.  Biol Trace Elem Res. 2008;  126 141-147
• 13 Amagase H, Petesch B L, Mtsuura H, Kasuga S, Itakura Y. Intake of garlic and its bioactive components.  J Nutr. 2001;  13 955-962
• 14 Miron T, Sivaraman H, Rabinkov A, Mirelman D, Wilchek M. A method for continuous production of allicin using immobilized allinase.  Anal Biochem. 2006;  351 152-154
• 15 Prasad K, Laxdal V A, Yu M, Raney B L. Antioxidant activity of allicin, an active principle in garlic.  Mol Cell Biochem. 1995;  148 183-189
• 16 Chung L Y. The antioxidant properties of garlic compounds: allyl cystein, alliin, allicin and allyl disulfide.  J Med Food. 2006;  9 205-213
• 17 Xu Z F, Jones M M. Comparative mobilization of lead by chelating agents.  Toxicology. 1988;  53 277-288
• 18 Pappas J B, Ahlquist J T, Allen E M, Banner W. Oral dimercaptosuccinic acid and ongoing exposure to lead: effects on heme synthesis and lead distribution in a rat model.  Toxicol Appl Pharmacol. 1995;  133 121-129
• 19 Pande M, Mehta A, Pant B P, Flora S J S. Combined administration of a chelating agent and an antioxidant in the prevention and treatment of acute lead intoxication in rats.  Environ Toxicol Phamacol. 2001;  9 173-184
• 20 Varnai V M, Piasek M, Blanusa M, Juresa D, Saric M, Kostial K. Ascorbic acid supplementation dose not improve efficacy of meso-dimercaptosuccinic acid treatment in lead-exposed suckling rats.  Pharmacol Toxicol. 2003;  93 180-185
• 21 Riess M L, Halm J K. Lead poisoning in an adult: lead mobilization by pregnancy?.  J Gen Intern Med. 2007;  22 1212-1215
• 22 Anderson O. Principles and recent developments in chelation treatment of metal intoxication.  Chem Rev. 1999;  99 2683-2710
• 23 Cory-Slechta D A, Weiss B, Coe C. Mobilization of lead over the course of calcium disodium ethylendiamine tetraacetate chelation therapy.  J Pharmacol Exp Ther. 1987;  293 804-813
• 24 Porru S, Alssio L. The use of chelating agents in occupational lead poisoning.  Occup Med. 1996;  46 41-48
• 25 Gurer H, Ercal N. Can antioxidants be beneficial in the treatment of lead poisoning?.  Free Radic Biol Med. 2000;  29 927-945
• 26 Foster B C, Foster M S, Vandenhoek S, Krantis A, Budzinski J W, Arnason J T, Gallicano K D, Choudri S. An in vitro evaluation of human cytochrom P450 3A4 and p-glycoprotein inhibition by garlic.  J Pharmacol Pharm Sci. 2001;  4 176-184
• 27 Freeman F, Kodera Y. Garlic chemistry: stability of s-(2-propenyl)2-propene-1-sulfinothioate (allicin) in blood, solvents, and simulated physiological fluids.  J Agric Food Chem. 1995;  43 2332-2338
• 28 Miron T, Bercovici T, Rabinkov A, Wilchek M, Mrelman D. Allicin: preparation and applications.  Anal Biochem. 2004;  331 364-369
• 29 Massadeh M M, Al-Safi S A, Momani I F, Alomary A A, Jaradat Q M, Alkofahi A S. Garlic (Allium sativum L.) as a potential antidote for cadmium and lead intoxication: cadmium and lead distribution and analysis in different mice organs.  Biol Trace Elem Res. 2007;  120 227-234
• 30 Senapati S K, Dey S, Dwivedi S K, Swarup D. Effect of garlic (Allium sativum L.) extract on tissue lead level in rats.  J Ethnopharmacol. 2001;  76 229-232
• 31 Hanafy M S, Shalaby S M, El-fouly M A, Abd el-Aziz M I, Soliman F A. Effect of garlic on lead contents in chicken tissue.  Dtsch Tierarztl Wochenschr. 1994;  101 157-158
• 32 Adegbesan B O, Adenuga G A. Effect of lead exposure on liver lipid peroxidative and antioxidant defense systems of protein-undernourished rats.  Biol Trace Elem Res. 2007;  116 219-225