Influence of Simultaneous Supplementation of Zinc and Copper During Chelation of Lead in Rats

Abstract

The influence of zinc and copper supplementation during chelation therapy to reduce zinc and copper imbalance and promote lead elimination from the body, was investigated in rats poisoned with lead. The simultaneous supplementation of zinc and copper increased urinary lead excretion by calcium disodium ethylenediamine tetraacetic acid (CaNa₂EDTA) compared to treatment with CaNa₂EDTA alone. Combination therapy was effective in potentiating the depletion of blood and renal lead by CaNa₂EDTA and meso 2,3-dimercapto succinic acid (DMSA). Combination therapy was also more effective in reducing hepatic lead by CaNa₂EDTA and blood lead by 2,3-dimercapto propane sulphonate (DMPS). Zinc and copper supplementation produced a more effective reversal of inhibited blood δ-aminolevulinic acid dehydratase (ALAD) activity, urinary δ-aminolevulinic acid excretion and depleted body zinc and copper status.

Get full access to this article

View all access options for this article.

References

Basinger MA , Jones MM & Tarka MP Relative efficacy of chelating agents as antidotes for acute nickel (II) acetate intoxication. Research Communication in Chemical Pathology and Pharmacology 1980; 30: 133-41.

Kostyniak PL & Clarkson TW Role of chelating agents in metal toxicity . Fundamental and Applied Toxicology 1981; 1: 367-80.

Cantilena LR & Klaassen CD The effects of chelating agents on the excretion of endogenous metals. Toxicology and Applied Pharmacology 1982; 63: 344-50.

Tandon SK , Jain VK & Mathur AK Effect of metal chelators on excretion and tissue level of essential trace elements. Environmental Research 1984; 35: 237-45.

McCall JT , Goldstein NP , Randall RV & Gross JB Comparative metabolism of copper and zinc in patients with Wilson's disease (hepatolenticular degeneration). American Journal of Medical Sciences 1967; 254: 13-23.

Scheuhammer AM & Cherian MG Influence of chronic MnCl2 and EDTA treatment on tissue level and urinary excretion of trace metals in rats . Archives of Environmental Contamination and Toxicology 1987; 11: 515-20.

Braide Vbc. Calcium EDTA toxicity: renal excretion of endogenous trace metals and the effect of repletion on collagen degradation in the rat. General Pharmacology 1984; 15: 37-41.

Miller CR , Zhu S-Y. , Victery W. & Goyer RA Partitioning of renal zinc between metallothionein and ethylenediaminetetra acetic acid (EDTA) and treatment of rats with CaNa2EDTA. Toxicology and Applied Pharmacology 1986; 84: 584-92.

Thomas DJ & Chisolm JJ Jr. Lead, zinc and copper decorporation during treatment of lead poisoned children with calcium disodium ethylenediaminetetraacetate treatment of lead poisoned children. Journal of Pharmacology and Experimental Therapeutics 1986; 239: 829-35.

10.

Sorenson Emb , Morretti ES & Lindebaum A. Chelation therapy and tissue distribution and excretion of lead in mice. Archives of Environmental Contamination and Toxicology 1980; 9: 619-26.

11.

Aronson AL & Hammond PB Effects of two chelating agents on the distribution and excretion of lead . Journal of Pharmacology & Experimental Therapeutics 1964; 146: 241-51.

12.

Proksch E. & Kolmel K. Zinkmangelsyndrom als Nebenwirkung von Chelatbildern. Deutsche Medizinische Wochenschrift 1985; 110: 1001-3.

13.

Swenerton Emb & Hurley LS Teratogenic effects of a chelating agent and their prevention by zinc. Science 1971; 173: 62-4.

14.

Kimmel CA Effect of route of administration on the toxicity and teratogenicity of EDTA in the rat. Toxicology and Applied Pharmacology 1977; 40: 299-306.

15.

Brownie CF , Brownie C. , Noden D. et al. Teratogenic effect of calcium edetate (CaEDTA) in rats and protective effect of zinc. Toxicology and Applied Pharmacology 1986; 82: 426-43.

16.

Flora Sjs & Tandon SK Beneficial effects of zinc supplementation during chelation treatment of lead intoxication in rats. Toxicology 1990; 64: 129-39.

17.

Flora Sjs , Dhawan M. & Tandon SK Influence of copper supplementation during chelation of lead. Clinical Chemistry and Enzymology Communications 1990; 3: 97-106.

18.

Berlin A. & Schaller KH European standardized method for the determination of δ-aminolevulinic acid dehydratase activity in blood. Zeitshrift Klinische Chemie und Klinische Biochemie 1974; 12: 389-90.

19.

Davis JR , Abrahams RH , Fishbein WI & Fabrega EA Urinary delta aminolevulinic acid (ALA) levels in lead poisoning II. correlation of ALA values with clinical findings in 250 children with suspected lead ingestion . Archives of Environmental Health 1986; 17: 164-71.

20.

Grandjean P. Occupational lead exposure in Denmark: screening with the hematofluorometer. British Journal of Industrial Medicine 1979; 36: 52-8.

21.

Kopito L. & Schwachman H. Determination of lead in urine by atomic absorption spectroscopy using co-precipitation with bismuth. Journal of Laboratory and Clinical Medicine 1967; 70: 326-32.

22.

Yeager DW , Cholak J. & Hendersen EW Determination of lead in biological and related material by atomic absorption spectrophotometry. Environmental Science and Technology 1971; 5: 1020-2.

23.

Parker MM , Humoller FL & Mahler DJ Determination of copper and zinc in biological material. Clinical Chemistry 1967; 13: 40-8.

24.

Victery W. , Miller CR & Goyer RA Essential trace metal excretion from rats with lead exposure and during chelation therapy. Journal of Laboratory and Clinical Medicine 1986; 107: 129-35.

25.

Finelli VN , Lerner S. , Hong C. & Lohiya G. Effect of zinc supplementation during chelation therapy in plumbism: a case report. Medical Lav 1980; 2: 149-56.

26.

Brownie CF & Aronson AL Comparative effects of Ca ethylenediamine tetraacetic acid (EDTA), ZnEDTA and Zn CaEDTA in mobilizing lead. Toxicology and Applied Pharmacology 1984; 75: 167-72.

27.

Thomas DJ & Chisolm JJ Jr. Lead, zinc and copper decorporation during treatment of lead poisoned children with calcium disodium ethylenediaminetetraacetate . Toxicologist 1986; 6: 49 (abstract 191).

28.

Kapoor SC , Wielopolski L. , Graziano JH & Lolacone NJ Influence of 2,3-dimercaptosuccinic acid on gastrointestinal lead absorption and whole body lead retention. Toxicology and Applied Pharmacology 1989; 97: 525-29.

29.

Graziano JH , Siris ES , Lolacone N. et al., 2,3-dimercaptosuccinic acid as an antidote for lead intoxication . Clinical Pharmacology and Therapeutics 1985 ; 37: 431-8.

30.

Cory-Slechta DA Mobilization of lead over the course of DMSA chelation therapy and long term efficacy. Journal of Pharmacology and Experimental Therapeutics 1988; 246: 84-91.

31.

Aposhian HV & Aposhian MM Meso-2,3-dimercaptosuccinic acid: chemical, pharmacological and toxicological properties of an orally effective metal chelating agent. Annual Review of Pharmacology and Toxicology 1990; 30: 279-306.

32.

Goering PL , Tandon SK & Klaassen CD Induction of hepatic metallothionein in mouse liver following administration of chelating agents. Toxicology and Applied Pharmacology 1985; 80: 467-72.

33.

Tewari PC , Flora Sjs & Tandon SK Distribution of cadmium in body organs and hepatic metallothionein contents following chelation therapy. Clinical and Experimental Pharmacology Physiology 1988; 15: 71-5.