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At least 145 records · Page 8Linked to original sources
PubMed1995

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.

Alkaline Phosphatase↗
PubMed1995

Antidotal efficacy of newly synthesized dimercaptosuccinic acid (DMSA) monoesters in experimental arsenic poisoning in mice.

The efficacy of four newly synthesized monoesters of meso-2,3-dimercaptosuccinic acid (DMSA), mono-i-amyl- (Mi-ADMS), mono-n-amyl- (Mn-ADMS), mono-i-butyl- (Mi-BDMS), and mono-n-butyl-meso-2,3-dimercaptosuccinate (Mn-BDMS) in increasing survival and arsenic elimination in experimental arsenic poisoning was investigated. Male mice (strain NMRI) received arsenite sc (survival study: 130 mumol/kg, 7 mice/group; elimination study: 85 mumol/kg (LD5) together with a tracer dose of 73As(III), 6 mice/group). After 30 min mice were treated with 0.7 mmol/kg of DMSA or a monoester ip or via gastric tube (ig). Control animals received saline ip. In the survival study mice were observed for 30 days. In the elimination study, the 73-arsenic content of several organs (blood, liver, heart, lung, kidneys, spleen, testes, brain, small intestine, large intestine, muscle, and skin) was measured 0.5, 2, 4, 6, and 8 hr after the arsenic injection using a gamma counter. Survival increased correspondingly well with the increase of arsenic elimination. DMSA, Mi-ADMS, Mn-ADMS, Mi-BDMS, and Mn-BDMS markedly decreased arsenic content in most organs as soon as 1.5 hr after treatment. Only in small and large intestine were higher arsenic amounts found, indicating a shift in arsenic elimination from the renal to the fecal route, and thereby suggesting a protective effect for the kidneys. Given ip, the monoesters turned out to be similarly as effective as the parent drug DMSA. Following ig treatment, the DMSA monoesters Mi-ADMS and Mn-ADMS seemed to be superior to DMSA with regard to survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Reversal of oxophenylarsine-induced inhibition of glucose uptake in MDCK cells.

It has been shown that oxophenylarsine (PhAsO) inhibits glucose uptake in MDCK cells. In addition to the known impairment of cellular energy metabolism, this inhibition may contribute to the acute toxicity of trivalent organic arsenicals. We have investigated the effect of BAL, DMPS, DMSA, and other sulfur compounds on cellular incorporation of [U-14C]PhAsO and their efficacy to revert PhAsO-induced inhibition of glucose uptake. In the presence of [U-14C]PhAsO (2 microM), the radiolabel was steadily accumulated by the cells over 150 min without any signs of severe cell damage (e.g., altered morphology, increased LDH release). A notable decrease of cellular ATP was only observed at 150 min, whereas within 30 min uptake of D-[6-(14)C]glucose was reduced to 40% of controls. When BAL, DMPS, or DMSA was added after 30 min, the inhibition of glucose uptake was reversed, accompanied by a decrease in cell-associated radiolabel from [U-14C]-PhAsO. Water-soluble DMPS and DMSA required longer times than BAL for comparable effects. 2,3-Bis(acetylthio)propanesulfonamide, a thioester derivative, and dithiothreitol, a 1,4-dithiol, were effective only with the highest concentration tested (200 microM). 2-Mercaptoethanol neither reversed inhibition of glucose uptake nor influenced [U-14C]PhAsO incorporation. Our results show that inhibition of glucose uptake is a very early event in PhAsO cytotoxicity which occurs before any decrease of cellular energy metabolism and/or full cellular loading with arsenic comes into effect. The more rapid onset of action of lipophilic BAL compared to PhAsO action.

Adenosine Triphosphate↗
PubMed1996

Chelation in metal intoxication. XXXVIII: Effect of structurally different chelating agents in treatment of nickel intoxication in rat.

Some structurally different chelating agents viz. alpha-mercapto-beta-(2-furyl) acrylic acid (MFA), alpha-mercapto-beta-(2-thienyl) acrylic acid (MTA), meso 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercaptopropane-1-sulfonate (DMPS), diethyl dithiocarbamate (DE-DTC), and N-benzyl-D-glucamine dithiocarbamate (NBG-DTC) were evaluated for their efficacy to mobilized nickel and reverse some nickel-induced biochemical alterations in experimental nickel intoxication. MFA, DMSA, and NBG-DTC appear more effective than their corresponding homologs, MTA, DMPS and DE-DTC, respectively, in enhancing urinary and fecal excretion of nickel and lowering tissue burden of nickel in nickel preexposed rats. These, particularly NBG-DTC, appear promising in the treatment of nickel (II) poisoning. However, there seems no definite relationship between the structure of the chelating agents examined and their ability to counteract the effects of nickel.

Acrylates↗
PubMed1993

Isolated rat kidney tubules as a screening system for arsenic antidotes.

Gluconeogenesis is one of the metabolic pathways severely affected in acute arsenic poisoning. We have studied gluconeogenesis in isolated kidney tubules of male Sprague-Dawley rats to screen various sulfur compounds for antidotal properties against inorganic and organic arsenicals. Freshly prepared kidney cells from starved rats synthesized glucose from added pyruvate (10 mmol/liter) at a rate of 9.74 +/- 0.90 nmol/min/mg protein (mean +/- SD; n = 61). Gluconeogenesis was inhibited almost 90% in the presence of phenylarsonate (700 mumol/liter), arsenate (350 mumol/liter), arsenite (30 mumol/liter), or PhAsO (1 mumol/liter). mumol/liter). With effective antidotes the rate of gluconeogenesis was restored to almost control values within 10 min. Among 21 sulfur compounds tested, only BAL, DMPS, and DMSA were effective in PhAsO poisoning. With inorganic arsenic also DTE and DTT restored the rate of glucose formation. The observed in vitro efficacies were in good agreement with in vivo results obtained with male NMRI mice severely poisoned with arsenite (As2O3, 20 mg/kg approximately 0.2 mmol As/kg) or PhAsO (3.4 mg/kg approximately 0.02 mmol As/kg). We conclude that isolated kidney tubules are a useful in vitro screening system (a) to compare the metabolic toxicity of various arsenicals and (b) to evaluate potential antidotes.

Animals↗
PubMed1995

Oral dimercaptosuccinic acid and ongoing exposure to lead: effects on heme synthesis and lead distribution in a rat model.

Lead (Pb) exposure and subsequent toxicity continues to be a significant problem in the United States. Treatment with meso-2,3-dimercaptosuccinic acid (DMSA) has been reported to be effective in reducing the body's Pb burden, with fewer adverse side effects than other chelating agents. The oral availability and relative safety of DMSA presents the controversial option of treating patients with Pb poisoning on an outpatient basis. Despite recommendations that children be removed from the Pb contaminated environment, some children will inevitably be exposed to environmental Pb while receiving oral DMSA therapy. The study hypothesized that oral DMSA chelation therapy is beneficial even when faced with continued dietary Pb. Sprague-Dawley rats were exposed to Pb in water for 35 days and then placed in various treatment groups, including groups administered oral DMSA with and without concurrent Pb exposure. The concentration of Pb in blood and critical organs and Pb diuresis were measured. The effect of Pb on heme synthesis was determined by assaying the urinary delta-aminolevulinic acid (delta-ALA), and blood zinc protoporphyrin (ZPP). DMSA reversed the hematological effects of Pb, decreased the blood, brain, bone, kidney, and liver Pb concentration, and produced a marked Pb diuresis, even when challenged with ongoing Pb exposure. In conclusion, even though DMSA treatment without exposure to Pb is optimal, oral DMSA could be beneficial even when challenged with ongoing Pb exposure.

Administration, Oral↗
PubMed1997

Effect of chelation with meso-dimercaptosuccinic acid (DMSA) before and after the appearance of lead-induced neurotoxicity in the rat.

This paper examines whether a chelating agent (DMSA) can prevent and reverse the effects of lead (Pb) as evidenced by changes in brain glial fibrillary acidic protein (GFAP) concentration and in the habituation pattern of rearing behavior. Male F344 rats (42 days old) received Pb acetate at 150 or 2000 ppm as Pb in their drinking water for 21 days and returned to regular water for another 21 days to observe recovery. Blood Pb (BPb) concentration rose to 37 and 82 microg/dl for 150 and 2000 ppm, respectively. Rats exposed to 150 ppm Pb exhibited changes in GFAP concentration and behavioral hyperactivity, when placed in an unfamiliar cage. The 2000 ppm Pb exposure caused greater changes in GFAP, but behavioral hyperactivity appeared only postexposure, when BPb was declining. Chelation (DMSA, 50 mg/kg po, 3 times/week for 21 days) decreased the BPb concentration, and prevented and reversed the Pb-induced changes in GFAP and rearing, but not in body weight. Administration of DMSA by itself for 21 days caused no untoward effects in brain GFAP, behavior, or body weight. Concurrent administration of DMSA and Pb resulted in no evidence of additive toxicity. Results indicate that: (1) A brief behavioral test of habituation is a sensitive index of neurotoxicity and chelating therapy; (2) Pb-induced hyperactivity depends upon BPb concentration regardless of whether activity is measured during or after exposure; (3) repeated treatment with DMSA is effective in reducing Pb neurotoxicity; (4) there was no evidence that DMSA enhanced the absorption of Pb. The finding that DMSA administered late in exposure can hasten the recovery of toxic signs suggests that extracellular Pb continues to play a significant role even after toxic signs have appeared.

Animals↗
PubMed1999

Vicinal-thiol-containing molecules enhance but mono-thiol-containing molecules reduce nickel-induced DNA strand breaks.

Several thiol-containing molecules (TCM) are currently used as antidotes for nickel, and vicinal TCM seem to be more effective in mobilizing tissue nickel than are mono TCM. Using single cell alkaline electrophoresis, we have shown that the vicinal TCM, meso-2, 3-dimercaptosuccinic acid (DMSA), 2,3-dimercaptopropane-1-sulfonate, and 2,3-dimercaptopropanol markedly enhanced, whereas the mono TCM, D-penicillamide, glutathione, beta-mercaptoethanol, and diethyl dithiocarbomate, reduced nickel chloride (Ni)-induced DNA breaks in a human leukemia cell line, NB4 cells. Ni or TCM alone did not induce plasmid DNA breaks in test tubes and neither did Ni plus mono TCM; however, Ni plus vicinal TCM did. Vicinal TCM did, but mono TCM did not generate H(2)O(2) in solution. H(2)O(2) alone did not, but H(2)O(2) plus Ni induced plasmid DNA breaks. Although Ni plus glutathione did not break DNA, Ni plus glutathione plus H(2)O(2) did. The Ni-DMSA-induced DNA breaks in NB4 cells, as well as in plasmids, were completely prevented by d-mannitol or partially prevented by several antioxidants. Therefore, the DNA breaks induced by Ni plus vicinal TCM seem to be due to the complex of Ni with TCM in concert with the H(2)O(2) produced by the vicinal TCM. The results that DMSA at a concentration as low as 5 microM enhanced the Ni-induced DNA breaks suggest a further evaluation of the TCM as nickel chelators is needed.

Cell Line↗
PubMed1991

Effects of chelating agents on the cadmium burden of cells in culture.

The effects of some new chelating agents on the cadmium burden of CHO cells in culture were investigated. The chelators were sodium-N-(4-methoxybenzyl)-D-glucamine-dithiocarbamate (MeOBG-DTC), sodium-N-benzyl-D-glucaminedithiocarbamate (BG-DTC) and diisopropylmeso-2,3-dimercapto succinate (DiP-DMSA). The results were compared with the effect of the well known dimercaptopropanol (BAL). The derivates of dithiocarbamate are much less toxic than DiP-DMSA and BAL. All chelators effectively prevent Cd uptake into the cells. Mobilization of intracellular Cd, however, is more effective by the DTC-derivatives than by DiP-DMSA or BAL. Within the cell the major fraction of Cd after 48 hours incubation is found in the nuclei and cytosol and very little in the peroxisomes. The chelating agents remove the metal mostly from nuclei and cytosol. Incubation of the cells with cadmium leads to the induction of a Cd binding protein of an apparent molecular weight of 12500 Da, presumably metallothionein. MeOBG-DTC is more effective in removing the metal from this protein than BG-DTC.

Animals↗
PubMed1995

Therapeutic potential of meso 2,3-dimercaptosuccinic acid or 2,3-dimercaptopropane 1-sulfonate in chronic arsenic intoxication in rats.

The therapeutic efficacy of two thiol chelators, meso 2,3-dimercaptosuccinic acid (DMSA) or 2,3-dimercaptopropane sulfonate (DMPS) in treating chronic arsenic intoxication was investigated in male rats. Both the chelators were effective in promoting urinary arsenic excretion and restoring arsenic induced inhibition of blood delta-aminolevulinic acid dehydratase activity and hepatic glutathione level. Elevation of urinary delta-aminolevulinic acid excretion and arsenic concentration in blood, liver and kidneys were reduced significantly by both the chelators. Histopathological lesions induced by arsenic were also effectively reduced by the above chelators. DMSA being more effective than DMPS. The results suggest DMSA and DMPS to be effective antidotes for treating chronic arsenic toxicity in experimental animals.

Animals↗
PubMed1992

Using technetium-99m (V) dimercaptosuccinic acid to detect malignancies from single solid masses in the lungs.

Fifty patients (43 male, 7 female, age 31-77 years) with single solid masses in their lungs based on the findings of a chest X-radiograph [40 malignancies: 5 small cell carcinoma (Ca), 17 epidermoid Ca, 12 adeno Ca, 6 undifferentiated large cell Ca] and 10 benign lesions underwent technetium-99m (V) dimercaptosuccinic acid [99m-(V)DMSA] scans to evaluate the usefulness of 99mTc-(V)DMSA in the detection of lung Ca with different cell types and benign lesions. Only 43% (17/40) of the malignancies in the lungs were detected by 99mTc-(V)DMSA, including 29% (5/17) epidermoid Ca, 50% (6/12) adeno Ca and 17% (1/6) undifferentiated large cell Ca of the lungs. However, all 5 cases of small cell Ca and 11 cases combined with bone metastasis were revealed by 99mTc-(V)DMSA. In addition, 3 of the 10 benign lesions (2 organizing pneumonias, 1 benign tumor) presented with an uptake of 99mTc-(V)DMSA. The diagnostic sensitivity, specificity and accuracy were 43%, 70% and 48%, respectively, in differentiating malignant from benign lesions for the single solid mass in the lungs. In conclusion, 99mTc-(V)DMSA is of little or no use in the differentiation of lung Ca from single solid masses in the lungs.

Adenocarcinoma↗
PubMed1992

Pitfalls in scintigraphic detection of neuroendocrine tumours.

We report 4 cases of abnormal results using iodine-123 metaiodobenzylguanidine (123I-mIBG) or technetium-99m (V) dimercaptosuccinic acid (99mTc(V)-DMSA) scintigraphy in the diagnosis and follow-up of presumed neuroendocrine tumours. The present series consisted of 2 false-positive cases (1 adenomatous polyp of the caecum with mIBG and 1 follicular adenoma of the thyroid with DMSA) and 2 cases of anomalous uptake of (V)-DMSA in a non-neuroendocrine tissue.

3-Iodobenzylguanidine↗
PubMed1991

Search for polynuclear pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS] tumour localization mechanism. I. Medullary thyroid carcinoma animal model.

To search for the tumour localization mechanism of Tc(V)-DMS, a polynuclear pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS], the development of medullary thyroid carcinoma (MTC) bearing mouse model was considered. Subcutaneously transplanted tumour was allowed to grow for 2, 4 and 6 weeks, and the influence of the tumour stage on the biodistribution of Tc(V)-DMS was screened. High radioactivity uptake in the tumour tissue was observed, and this accumulation showed a direct correlation with tumour growth and calcitonin secretion, the MTC marker detectable in the blood serum. The gathered data implicated some calcitonin-related factors as the mediator in the Tc(V)-DMS localization; participation of a phosphate-like oxoanion, TcO4(3-), is strongly suggested not only by the high radioactivity accumulation in the calcitonin-producing tumour but also by the accumulation in the bones of this model animal.

Animals↗
PubMed1992

Technetium-99m diethylene triamine penta-acetic acid and dimercaptosuccinic acid in the detection of a segmental branch stenosis of the renal artery by captopril renography.

We present a case in which a 39-year-old woman with correctable bilateral renovascular hypertension did not show abnormality during post-captopril technetium-99m dimercaptosuccinic acid (DMSA) study. Post-captopril 99mTc-diethylene triamine penta-acetic acid (DTPA) scintigraphy revealed the adverse effect of a stenosis of the artery supplying the upper part of her left kidney but failed to uncover the existence of severe multiple narrowings of the right renal artery. After bilateral renovascular reconstructive surgery, the hypertension completely disappeared. This case illustrates that DTPA may be more efficacious than DMSA in the detection of segmental loss of renal function induced by angiotensin converting enzyme inhibition.

Adult↗
PubMed1993

Hypertension in paediatrics: can pre- and post-captopril technetium-99m dimercaptosuccinic acid renal scans exclude renovascular disease?

In children over 1 year of age, renal disease is the commonest cause of hypertension. Arteriography is considered the reference method to establish the diagnosis of renovascular disease; however, it is an invasive technique with a high radiation burden for children. This was a retrospective study of pre- and post-capto-technetium-99m dimercaptosuccinic acid (DMSA) imaging compared with arteriography in 18 children between the ages of 3 and 17 years. Alone, the 99mTc-DMSA scan is a sensitive indicator of renal parenchymal disease, although non-specific in suggesting the pathology. The combination of pre- and post-captopril studies may increase the sensitivity and specificity in the diagnosis of renovascular disease in the presence of hypertension. This work suggests that a screening investigation with a low radiation burden can be carried out at most institutions; if the investigation is positive, there will be a high index of suspicion that renovascular disease is the cause of the hypertension.

Adolescent↗
PubMed1994

Estimation of normal chromium-51 ethylene diamine tetra-acetic acid clearance in children.

In order to estimate the normal range of chromium-51 ethylene diamine tetra-acetic acid (EDTA) clearance in children, we selected a series of 256 patients with past or present urinary tract infection who showed, at the time of the clearance determination, normal technetium-99m dimercaptosuccinic acid (DMSA) scintigraphy and normal left to right DMSA relative uptake. The clearance was calculated by means of either the simplified second exponential method or the 120-min single blood sample; Chantler's correction was used in order to correct for having neglected the first exponential. There was a progressive increase in clearance from the first weeks of life (mean value around 1 month: 55 ml/min/1.73 m2), with a plateau at around 18 months. Between 2 and 17 years of age, the clearance values remained constant, with a mean value of 114 ml/min/1.73 m2 (SD: 24 ml/min); this is similar to the level described for inulin clearance. No significant differences were observed between boys and girls, or between clearance values calculated with one or with two blood samples. Taking into account the hour of intravenous injection of the tracer, we did not observe any influence of the lunchtime meal on the distribution of the 51Cr-EDTA clearance values.

Adolescent↗