Combined therapeutic potential of meso-2,3-dimercaptosuccinic acid and calcium disodium edetate on the mobilization and distribution of lead in experimental lead intoxication in rats.
Asymptomatic lead poisoning remains a serious public health problem in developed and developing countries. Chelation therapy particularly with calcium disodium ethelenediamine tetracetic acid (CaNa2EDTA) is often used therapeutically to reduce the body burden of lead. This chelating drug has serious side effects and drawbacks primarily related to redistribution of lead, nephrotoxicity, and essential metal depletion. The present study was planned to determine the effectiveness of CaNa2EDTA and meso-2,3-dimercaptosuccinic acid (DMSA) used in combination. Both drugs, when administered individually, resulted in significant urinary excretion of lead and lowered the tissue lead burden. Combined treatment with CaNa2EDTA and DMSA elicits an additive response in promoting urinary lead elimination, depleting body lead burden, and restoring altered lead-sensitive biochemical variables. Further, no redistribution of lead to brain or any other soft organ following combined DMSA-CaNa2EDTA treatment was observed indicating a definite advantage of combined therapy over the conventional treatment with CaNa2EDTA or DMSA alone. However, an elevation of serum transaminase activity, creatinine level, and depletion of blood zinc level may limit the usefulness of this combined treatment.
Flora
S J
SJ
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India.
Bhattacharya
R
R
Vijayaraghavan
R
R
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001923:Brain Chemistry; D003300:Copper / Q000032:analysis / Q000097:blood; D004359:Drug Therapy, Combination; D004492:Edetic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D005269:Femur / Q000737:chemistry; D007668:Kidney / Q000737:chemistry; D007854:Lead / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D007855:Lead Poisoning / Q000188:drug therapy*; D008099:Liver / Q000737:chemistry; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D004113:Succimer / Q000494:pharmacology / Q000627:therapeutic use*; D000637:Transaminases / Q000097:blood; D015032:Zinc / Q000032:analysis / Q000097:blood
D007854:Lead; D003300:Copper; D004492:Edetic Acid; D004113:Succimer; D000637:Transaminases; D000469:Alkaline Phosphatase; D015032:Zinc