Combined treatment withracemic-DMSA and EDTA for lead mobilization in rats

Kostial, Krista; ija, Nada Restek-Samar; Piasek, Martina; Varnai, Veda Marija; a, Maja Blanu; Jones, Mark M.; Singh, Pramod K.

doi:10.1002/1520-670x(2000)13:3<277::aid-jtra5>3.0.co;2-2

Cited by 6 publications

(3 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results of combined treatments with CaNa 2 EDTA and the two thiols were more impressive both in terms of recovery in altered biochemical variables (oxidative stress) and reduction of body lead burden. There have been recent debates about introducing combined treatment therapy for lead poisoning [22,74,75]. The two arguments proposed for promoting this treatment point to the fact that (i) the inefficiency of EDTA to decrease brain lead and the ability of thiol chelators like DMSA for their reported role in promoting soft tissue lead mobilization including brain and (ii) addition of MiADMSA to EDTA caused not only higher lead elimination but also better recovery in altered biochemical variables.…”

Section: Discussionmentioning

confidence: 99%

Lead‐induced oxidative stress and hematological alterations and their response to combined administration of calcium disodium EDTA with a thiol chelator in rats

Saxena

Flora

2004

J Biochem & Molecular Tox

103

View full text Add to dashboard Cite

The therapeutic efficacy of calcium disodium ethylenediaminetetracetic acid (CaNa(2)EDTA) and the two thiol chelators, 2,3-dimercaptopropane 1-sulfonate (DMPS) and monoisoamyl dimercaptosuccinic acid (MiADMSA) was studied, both individually and in combination, in reducing lead concentration in blood and soft tissues and in restoring lead induced altered biochemical variables in rats. Exposure to subacute dose of lead implicated a critical role of reactive oxygen species (ROS) and oxidative stress in altering the normal values of these variables. Exposure to lead caused a significant inhibition of blood delta-aminolevulinic acid dehydratase (ALAD), an important enzyme in the haem synthesis pathway and glutathione (GSH) level. These changes were also accompanied by inhibition of ALAD activity in kidney, delta-aminolevulinic acid synthase (ALAS) activities in liver and changes in platelet counts in whole blood suggesting disturbed haem synthesis pathway. Lead exposure also led to a pronounced depletion of brain GSH contents, superoxide dismutase (SOD) activity, an increase in thiobarbituric acid reactive substances (TBARS), and activity of glutathione S-transferase (GST). Specific activities of membrane-bound enzymes, acetylcholinesterase (AChE) and monoamine oxidase (MAO), were significantly inhibited on lead exposure. These biochemical changes were correlated with increased uptake of lead in blood and soft tissues. Post lead exposure treatment with MiADMSA in particular provided significant recovery in altered biochemical variables besides significant depletion of tissue lead burden. Treatment with CaNa(2)EDTA and DMPS individually had only moderate beneficial effects on tissue oxidative stress, although they were equally effective in the removal of tissue lead burden. Tissue zinc and copper levels did not depict any significant depletion, although changes like marked depletion of zinc following CaNa(2)EDTA and copper after MiADMSA administration were of some concern. Combined administration of CaNa(2)EDTA, particularly with MiADMSA, was the most effective treatment protocol compared to all other treatments. It can be concluded from our present results that combined therapy with CaNa(2)EDTA and MiADMSA proved significantly better in restoring biochemical and clinical variables over monotherapy with these chelating agents against subacute lead exposure in adult rats.

show abstract

Section: Discussionmentioning

confidence: 99%

Lead‐induced oxidative stress and hematological alterations and their response to combined administration of calcium disodium EDTA with a thiol chelator in rats

Saxena

Flora

2004

J Biochem & Molecular Tox

103

View full text Add to dashboard Cite

show abstract

“…This study showed that the combination of CaNa 2 EDTA plus rac-DMSA is more efficient in removing lead from bone and kidney than the combination of CaNa 2 EDTA plus meso-DMSA. However, this combination also caused highest trace element (copper, zinc, and iron) elimination in the urine [340]. The same combination of chelators was applied to reduce tissue lead concentrations in suckling rats.…”

Section: Derivatives Of Bal: Dmps Dmsa and Its Monoand Dialkylestersmentioning

confidence: 99%

Chelators as Antidotes of Metal Toxicity: Therapeutic and Experimental Aspects

Blanuša¹,

Varnai²,

Piasek³

et al. 2005

CMC

Self Cite

240

150

View full text Add to dashboard Cite

The effects of chelating drugs used clinically as antidotes to metal toxicity are reviewed. Human exposure to a number of metals such as lead, cadmium, mercury, manganese, aluminum, iron, copper, thallium, arsenic, chromium, nickel and platinum may lead to toxic effects, which are different for each metal. Similarly the pharmacokinetic data, clinical use and adverse effects of most of the chelating drugs used in human metal poisoning are also different for each chelating drug. The chelating drugs with worldwide application are dimercaprol (BAL), succimer (meso-DMSA), unithiol (DMPS), D-penicillamine (DPA), N-acetyl-D-penicillamine (NAPA), calcium disodium ethylenediaminetetraacetate (CaNa(2)EDTA), calcium trisodium or zinc trisodium diethylenetriaminepentaacetate (CaNa(3)DTPA, ZnNa(3)DTPA), deferoxamine (DFO), deferiprone (L1), triethylenetetraamine (trientine), N-acetylcysteine (NAC), and Prussian blue (PB). Several new synthetic homologues and experimental chelating agents have been designed and tested in vivo for their metal binding effects. These include three groups of synthetic chelators, namely the polyaminopolycarboxylic acids (EDTA and DTPA), the derivatives of BAL (DMPS, DMSA and mono- and dialkylesters of DMSA) and the carbodithioates. Many factors have been shown to affect the efficacy of the chelation treatment in metal poisoning. Within this context it has been shown in experiments using young and adult animals that metal toxicity and chelation effects could be influenced by age. These findings may have a bearing in the design of new therapeutic chelation protocols for metal toxicity.

show abstract

“…Recently succimer) is an orally active chelating agent approved for treatment of lead poisoning in children with blood lead levels above 45 µg dl −1 (Committee on Drugs, 1995;Piomelli, 2002). In order to increase the treatment efficacy, attempts have been made to combine DMSA with other chelating agents (Flora et al, 1995;Tandon et al, 1998;Kostial et al, 1999Kostial et al, , 2000, vitamins (Dhawan et al, 1988;Tandon & Flora, 1989), antioxidants (Pande et al, 2001;Pande & Flora, 2002;Tandon et al, 2002) and minerals (Flora et al, 1998), with various success.…”

mentioning

confidence: 99%

Succimer treatment and calcium supplementation reduce tissue lead in suckling rats

Varnai¹,

Piasek²,

Blanuša³

et al. 2004

J of Applied Toxicology

Self Cite

View full text Add to dashboard Cite

The effect of combined treatment with meso-2,3-dimercaptosuccinic acid (DMSA) and calcium supplementation in reducing lead absorption and enhancing lead elimination was evaluated in suckling rats under two experimental conditions: during ongoing oral lead exposure (lead acetate, 2 mg Pb kg(-1) day(-1), total dose 16 mg Pb kg(-1)) or after lead exposure (72 h after a 2-day lead exposure, total dose 12 mg Pb kg(-1) s.c.). The artificial feeding method was used for calcium supplementation, with 6% Ca (as CaHPO(4)) suspension in cow's milk to increase the daily calcium intake about three times above control values. Artificial feeding lasted for 7 h a day over eight consecutive days. During this period DMSA was administered on 6 days twice a day (0.5 mmol kg(-1) day(-1) p.o.). At the end of the experiments, Pb, Ca and Zn in the carcass and Pb, Fe and Cu in the liver, kidneys and brain were analysed by atomic absorption spectrometry. Calcium supplementation during lead exposure reduced tissue lead but had no effect when applied after lead exposure, and DMSA administered either during or after lead exposure lowered the tissue lead. Combined treatment during ongoing lead exposure caused a greater reduction in tissue lead than either DMSA or calcium treatment alone. When administered after lead exposure, it had no advantage over DMSA treatment alone but did not impair its efficacy. Combined treatment had no influence on growth and did not seriously disturb essential element status. It is concluded that calcium supplementation could be applied during DMSA therapy, when indicated.

show abstract

Combined treatment withracemic-DMSA and EDTA for lead mobilization in rats

Cited by 6 publications

References 17 publications

Lead‐induced oxidative stress and hematological alterations and their response to combined administration of calcium disodium EDTA with a thiol chelator in rats

Lead‐induced oxidative stress and hematological alterations and their response to combined administration of calcium disodium EDTA with a thiol chelator in rats

Chelators as Antidotes of Metal Toxicity: Therapeutic and Experimental Aspects

Succimer treatment and calcium supplementation reduce tissue lead in suckling rats

Contact Info

Product

Resources

About