succimer and Body-Weight

Growth deficits associated with lead exposure might be ameliorated by chelation. We examined the effect of succimer on growth in 780 children 12-33 months old who had blood lead levels of 20-44 microg/dL and were randomized to receive up to three 26-day courses of succimer or placebo in a multicenter, double-blind trial. The difference in changes in weight and height between succimer and placebo groups at 1-34 months was calculated by fitting cubic splines. The difference in height change in children on succimer compared with placebo was -0.27 cm [95% confidence interval (95% CI), -0.42 to -0.11] from baseline to 9 months, when 99% of children had completed treatment, and -0.43 cm (95% CI, -0.77 to -0.09) during 34 months of follow-up. Similar differences in weight gain were not statistically significant. Although succimer lowers blood lead in moderately lead-poisoned children, it does not have a beneficial effect on growth and may have an adverse effect.

Topics: Body Height; Body Weight; Chelating Agents; Child Development; Double-Blind Method; Female; Growth; Humans; Infant; Lead Poisoning; Male; Placebos; Succimer; Treatment Outcome

Combination therapy can play a significant role in the amelioration of several toxic effects of lead (Pb) and recovery from associated cardiovascular changes.. To investigate the effects of combination therapy on the cardiovascular effects of perinatal lead exposure in young and adult rats Methods: Female Wistar rats received drinking water with or without 500 ppm of Pb during pregnancy and lactation. Twenty-two- and 70-day-old rat offspring who were or were not exposed to Pb in the perinatal period received meso-dimercaptosuccinic acid (DMSA), L-arginine, or enalapril and a combination of these compounds for 30 additional days. Noradrenaline response curves were plotted for intact and denuded aortas from 23-, 52-, 70-, and 100-day-old rats stratified by perinatal Pb exposure (exposed/unexposed) and treatment received (treated/untreated).. Systolic blood pressure was evaluated and shown to be higher in the 23-, 52-, 70-, and 100-day age groups with Pb exposure than in the corresponding control age groups: 117.8 ± 3.9*, 135.2 ± 1.3*, 139.6 ± 1.6*, and 131.7 ± 2.8*, respectively and 107.1 ± 1.8, 118.8 ± 2.1, 126.1 ± 1.1, and 120.5 ± 2.2, respectively (p < 0.05). Increased reactivity to noradrenaline was observed in intact, but not denuded, aortas from 52-, 70-, and 100-day-old exposed rats, and the maximum responses (g of tension) in the respective Pb-exposed and control age groups were as follows: 3.43 ± 0.16*, 4.32 ± 0.18*, and 4.21 ± 0.23*, respectively and 2.38 ± 0.33, 3.37 ± 0.13, and 3.22 ± 0.21, respectively (p < 0.05).. All treatments reversed the changes in vascular reactivity to noradrenaline in rats perinatally exposed to Pb. The combination therapy resulted in an earlier restoration of blood pressure in Pb-exposed rats compared with the monotherapies, except for enalapril therapy in young rats. These findings represent a new approach to the development of therapeutic protocols for the treatment of Pb-induced hypertension.

Topics: Age Factors; Animals; Antihypertensive Agents; Arginine; Blood Pressure; Body Weight; Cardiovascular System; Chelating Agents; Combined Modality Therapy; Enalapril; Female; Hypertension; Lactation; Lead; Lead Poisoning; Male; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Wistar; Succimer; Time Factors; Treatment Outcome

Cadmium (Cd) is a heavy metal which causes concern as an environmental toxicant. Therapy with chelating agents is considered to be the rational treatment against metal poisoning. This study was designed to evaluate whether meso-2,3-dimercaptosuccinic acid (DMSA) could alleviate oxidative stress and vascular dysfunction in mice with subchronic exposure to Cd. Male ICR mice received CdCl2 (100 mg/L) via drinking water for 8 weeks. After Cd exposure, DMSA at a dose of 25 mg/kg or 50 mg/kg was intragastrically administered once daily for 5 consecutive days at the end of Cd treatment. It was found that Cd-induced hypertension and markedly blunted vascular responses to vasoactive agents, including acetylcholine, phenylephrine and sodium nitroprusside. Treatment with DMSA significantly restored blood pressure and improved vascular responsiveness when compared with Cd-treated controls. Moreover, DMSA protected against Cd-induced severe oxidative stress by normalization of the redox ratios of glutathione to glutathione disulfide and suppression of plasma malondialdehyde, plasma protein carbonyl, urinary nitrate/nitrite, and superoxide production from thoracic aorta. DMSA partially reduced Cd contents in the blood, heart, liver and kidneys. In conclusion, our present study provides the first evidence of the therapeutic efficacy of DMSA against oxidative stress and vascular dysfunction in Cd-intoxicated mice.

Topics: Animals; Blood Pressure; Body Weight; Cadmium; Chelating Agents; Environmental Pollutants; Hemodynamics; Male; Mice; Mice, Inbred ICR; Organ Size; Oxidative Stress; Succimer; Vascular Diseases

The present study reports on the preparation and testing of a desoxycholate amphotericin B (D-AMB) sustained delivery system based on poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) polymeric blends (Nano-D-AMB) aimed at reducing the number of AMB administrations required to treat mycosis.. BALB/c mice were infected with the yeast Paracoccidioides brasiliensis intravenously to mimic the chronic form of paracoccidioidomycosis. At 30 days post-infection, the animals were treated with Nano-D-AMB [6 mg/kg of encapsulated D-AMB, intraperitoneally (ip), interval of 72 h] or D-AMB (2 mg/kg, ip, interval of 24 h). Drug efficacy was investigated by the fungal burden recovery from tissues. Toxicity was assessed by renal and hepatic biochemical parameters, physical appearance of the animals and haematological investigation. The control groups used were non-infected and the infected mice mock treated with PBS.. Nano-D-AMB presented results comparable to free D-AMB, with a marked antifungal efficacy. The Nano-D-AMB-treated group presented lower loss of body weight and absence of stress sign (piloerection and hypotrichosis) observed after D-AMB treatment. No renal [blood urea nitrogen (BUN), creatinine] or hepatic (pyruvic and oxalacetic glutamic transaminases) biochemical abnormalities were found. The micronucleus assay showed no significant differences in both the micronucleus frequency and percentage of polychromatic erythrocytes for Nano-D-AMB, indicating the absence of genotoxicity and cytotoxic effects.. The D-AMB-coated PLGA-DMSA nanoparticle showed antifungal efficacy, fewer undesirable effects and a favourable extended dosing interval. Nano-D-AMB comprises an AMB formulation able to lessen the number of drug administrations. Further studies would elucidate whether Nano-D-AMB would be useful to treat systemic fungal infections such as paracoccidioidomycosis, candidiasis, aspergillosis and cryptococcosis.

Topics: Amphotericin B; Animals; Body Weight; Bone Marrow; Colony Count, Microbial; Deoxycholic Acid; Drug Combinations; Female; Kidney; Lactic Acid; Liver; Lung; Mice; Mice, Inbred BALB C; Nanoparticles; Paracoccidioides; Paracoccidioidomycosis; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Succimer; Treatment Outcome

Arsenic contamination of groundwater in the West Bengal basin in India is unfolding as one of the worst natural geo-environmental disasters to date. Chelation therapy with chelating agents is considered to be the best known treatment against arsenic poisoning; however, they are compromised with certain serious drawbacks/side-effects. Efficacy of combined administration of Moringa oleifera (M. oleifera) (English: Drumstick tree) seed powder, a herbal extract, with a thiol chelator monoisoamyl DMSA (MiADMSA) post-arsenic exposure in mice was studied. Mice were exposed to 100 ppm arsenic in drinking water for 6 months, followed by 10-days treatment with M. oleifera seed powder (500 mg/kg, orally through gastric gavage, once daily), MiADMSA (50 mg/kg, intraperitoneally, once daily) either individually or in combination. Arsenic exposure caused significant decrease in blood glutathione, delta-aminolevulinic acid dehydratase (ALAD), accompanied by increased production of reactive oxygen species in blood and soft tissues. Significant inhibition of superoxide dismutase, catalase, and glutathione peroxidase activities in tissues (liver in particular) along with significant increase in thiobarbituric acid reactive substances and metallothionein levels in arsenic intoxicated mice was also noted. Combined administration of MiADMSA with M. oleifera proved better than all other treatments in the recovery of most of the above parameters accompanied by more pronounced depletion of arsenic. The results suggest that concomitant administration of M. oleifera during chelation treatment with MiADMSA might be a better treatment option than monotherapy with the thiol chelator in chronic arsenic toxicity.

Topics: Animals; Antioxidants; Arsenic; Arsenic Poisoning; Body Weight; Brain; Chelating Agents; Drinking; Eating; Free Radicals; Glutathione; Kidney; Liver; Male; Metals; Mice; Moringa oleifera; Oxidative Stress; Seeds; Succimer; Tissue Distribution

To examine the effects of meso-2,3-dimercaptosuccinic acid (DMSA) on developmental toxicity resulting from exposure to lead in utero, female albino mice were exposed to lead by drinking water contaminated with lead acetate for 4 weeks. After the cessation of lead exposure, female mice were supplemented by gavage with saline solution, DMSA, or DMSA and calcium as well as ascorbic acid from the fourth day of gestation until parturition, respectively. Lead levels (blood, liver, and bone) were measured at birth. Pups were then tested about neural development including surface righting reflex, cliff avoidance and air righting reflex. The markers of physical maturation, such as body weight, pinna unfolding, incisor eruption, and eye opening were also recorded. DMSA treatment decreased blood lead levels of pregnant mice, however, increased lead levels in both liver and bone of fetus, and delayed the early physical and neural development of offspring. Calcium and ascorbic acid reduced the transfer of lead to fetus. In conclusion, DMSA treatment during pregnancy enhances lead-induced fetal developmental toxicity.

Topics: Animals; Ascorbic Acid; Body Burden; Body Weight; Calcium Carbonate; Chelating Agents; Female; Fetal Development; Growth; Hemoglobins; Lead; Male; Mice; Nervous System; Pregnancy; Succimer

Two chelating agents meso-2,3-dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercapto-propane-1-sulphonate (DMPS) were tested for their efficiency in mercury removal from the body of rats in the presence and in the absence of selenium. Female Wistar rats were given a single intraperitoneal injection of mercuric chloride or an equimolar mixture of mercuric chloride and sodium selenite (1.5 micromol/kg body weight). The chelating agents were given orally, in excess (500 micromol DMSA/kg body weight; 300 micromol DMPS/kg body weight), 30 min after the administration of mercury and selenium. The animals were euthanized 24 h after the treatment and mercury in the kidney, liver, and 24 h urine was determined using cold vapour atomic absorption spectrometry (CV-AAS). The simultaneous administration of mercuric chloride and sodium selenite led to a redistribution of mercury in the organs, so that accumulation of mercury in the kidneys was decreased and in the liver increased. Selenite also caused decrease in the level of urinary mercury excretion. Both chelating agents were effective in mercury removal from the body, by increasing its urinary excretion. However, when animals were simultaneously treated with mercury and selenite, the rise of mercury excreted in the urine due to the treatment with chelating agents was lower when compared to animals receiving mercury without selenite. It is concluded that sodium selenite decreases the efficiency of DMSA and DMPS in mercury removal from the body of rats.

Topics: Animals; Antidotes; Body Weight; Chelating Agents; Female; Kidney; Liver; Mercuric Chloride; Mercury; Organ Size; Proteins; Rats; Rats, Wistar; Selenium; Selenoproteins; Sodium Selenite; Spectrophotometry, Atomic; Succimer; Unithiol

Oral chelation tests have been used to try to define mercury toxicity in individuals with dental amalgams, who are suffering from a variety of non-specific symptoms.. Self-reported healthy individuals volunteered to undergo an oral chelation test using dimercaptosuccinic acid (DMSA) at a dose of 30 mg/kg body weight. Urinary mercury : creatinine ratios were measured pre-dose and 3 h post-dose.. Urinary mercury : creatinine ratios were similar to levels previously reported in individuals with symptoms that could have been attributed to mercury toxicity. One volunteer suffered a serious reaction to DMSA.. The oral chelation test using DMSA may lead to misleading diagnostic advice regarding potential mercury toxicity and can be associated with serious side effects.

Topics: Administration, Oral; Adult; Body Weight; Case-Control Studies; Chelating Agents; Creatinine; Dental Amalgam; Healthy People Programs; Humans; Mercury; Mercury Poisoning; Middle Aged; Succimer

The combined therapeutic potentials of lipoic acid and dimercaptosuccinic acid were compared against their sole administrations in restoring the altered lead sensitive indices in urine and isolated renal brush-border preparations. Toxicity was induced in male albino rats (Wistar strain) by administering lead acetate (0.2%) in drinking water for 5 weeks, followed by therapy comprising lipoic acid (25 mg/kg body weight) and dimercaptosuccinic acid (20 mg/kg body weight) solely as well as combined during the 6th week. Changes in kidney weights encountered upon lead administration improved after therapy with lipoic acid and dimercaptosuccinic acid. Renal integrity was assessed by measuring the activities of alkaline phosphatase, acid phosphatase, lactate dehydrogenase, leucine aminopeptidase, N-acetyl-beta-D-glucosaminidase, gamma-glutamyl transferase and beta-glucuronidase in urine along with some urinary constituents (urea, uric acid, creatinine, protein and phosphorous). The effects of lead were also studied on isolated brush-border enzymes (alkaline phosphatase, acid phosphatase, gamma-glutamyl transferase and beta-glucuronidase) that showed a decline upon its administration. Increased activities of urinary enzymes were accompanied by increase in the urinary constituents. Increase in renal lead content was paralleled by a drastic fall in the renal delta-aminolevulinic acid dehydratase and a rise in urinary lead levels. Relative to the administration of lead, the combined therapy showed betterment on the renal integrity with respect to the functional parameters assessed, thereby indicating its efficacy over the monotherapies.

Topics: 5-Aminolevulinate Synthetase; Animals; Antioxidants; Biomarkers; Body Weight; Chelating Agents; Disease Models, Animal; Drug Therapy, Combination; Kidney Cortex; Kidney Diseases; Kidney Tubules; Lead Poisoning; Male; Microvilli; Organ Size; Organometallic Compounds; Rats; Rats, Wistar; Succimer; Thioctic Acid

Seventy-two female rhesus monkeys were randomly assigned to three lead exposure conditions (none, birth to 1 year, birth to 2 years). In a completely crossed design, the lead-exposed and control monkeys were randomized to placebo or chelation therapy which began at 1 year of age. Dosing was conducted daily beginning on day 8 postpartum. The lead dose levels were adjusted biweekly to gradually elevate the blood lead level of each monkey to a target of 1.69-1.93 micromol/L (35-40 microg/dL). Succimer (or placebo) was administered orally (30 mg/kg/day for 5 days and 20 mg/kg/day for 14 additional days) for a total 19-day treatment regimen. There were two separate chelation regimes at 53 and 65 weeks of age. Succimer therapy in combination with lead abatement reduced blood lead levels significantly faster than lead abatement alone; however, that advantage disappeared once succimer therapy was discontinued. Weight, crown-rump length, and head circumference were measured regularly. Growth in weight, length, and head circumference did not vary significantly as a function of blood lead levels. Succimer chelation therapy did not significantly affect weight, length, or head circumference through 2 years of age.

Topics: Administration, Oral; Animals; Body Height; Body Weight; Chelating Agents; Cross-Over Studies; Environmental Exposure; Female; Lead; Lead Poisoning; Macaca mulatta; Random Allocation; Succimer; Treatment Outcome

To compare efficacy and safety of meso-2,3-dimercaptosuccinic acid (DMSA) and Ca EDTA for treatment of experimentally induced lead toxicosis in cockatiels (Nymphicus hollandicus).. 137 (69 females, 68 males) healthy cockatiels between 6 months and 8 years old.. Lead toxicosis was induced by placing lead shot in the gastrointestinal tract. Treatment with Ca EDTA (40 mg/kg of body weight, IM, q 12 h), DMSA (40 or 80 mg/kg, PO, q 12 h), and sodium sulfate salts (SSS; 0.5 mg/kg, PO, q 48 h) was initiated 4 days after induction of lead toxicosis. Blood lead concentrations were determined, using atomic absorption spectrophotometry. Number of birds surviving and blood lead concentrations were compared among groups.. In Phase II of the study, administration of DMSA and Ca EDTA significantly decreased blood lead concentrations when used alone or in combination in birds with lead toxicosis. Addition of SSS did not result in further decreases in lead concentrations. Eight of 12 (66.7%) birds without lead toxicosis given 80 mg of DMSA/kg did not survive to the end of the study. Lesions related to treatment with chelating agents were not detected during necropsy.. DMSA and Ca EDTA are effective chelating agents in cockatiels. Because DMSA is administered orally, it may be easier than other chelating agents for bird owners to administer at home. However, the narrow margin of safety of DMSA indicates that this agent should be used with caution.

Topics: Animals; Bird Diseases; Body Weight; Chelating Agents; Edetic Acid; Female; Kidney; Lead; Lead Poisoning; Liver; Male; Psittaciformes; Random Allocation; Spectrophotometry, Atomic; Spleen; Succimer; Survival Analysis; Thyroid Gland

Comparison of the racemic and meso forms of 2,3-dimercaptosuccinic acid (DMSA) in lead mobilization from lead-loaded albino Wistar rats demonstrates that the racemic form is significantly more effective in reducing femur lead levels. After four oral doses at 0.5 mmol/kg, femur lead levels were reduced to 87% of control values by meso-DMSA and to 50% of control levels by rac-DMSA. Similarly, when the dose was increased to 1.0 mmol/kg, femur lead levels were reduced to 69% of control levels by meso-DMSA and to 45% of control levels by rac-DMSA. A similar pattern was found for renal lead levels. Brain lead concentrations were significantly lower in treated groups than in control groups, but no differences were found between rac- and meso-DMSA. Rac-DMSA is more soluble than meso-DMSA in acetonitrile, ethyl acetate, and ethyl ether. The partition coefficient of rac-DMSA in the n-octanol/water system was found to be about 2.8. These results indicate that rac-DMSA deserves further attention as a possible substitute for meso-DMSA.

Topics: Animals; Body Weight; Brain Chemistry; Female; Femur; Kidney; Lead; Liver; Rats; Rats, Wistar; Stereoisomerism; Succimer

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.

Topics: Animals; Behavior, Animal; Body Weight; Brain Chemistry; Central Nervous System Diseases; Chelating Agents; Drinking; Glial Fibrillary Acidic Protein; Lead; Male; Rats; Rats, Inbred F344; Succimer

Radiation dosimetry was performed on 24 children (aged 5 wk to 14.8 yr) who were undergoing routine diagnostic investigation of renal impairment with 99mTc-DMSA.. Organ doses were calculated using MIRDOSE 3 with biokinetic data obtained in previously described studies, and effective doses and effective dose equivalents were estimated. Interpolation by inverse weight between pediatric anthropomorphic phantoms was compared with age-matching to discrete phantoms. Administered activities were scaled by body surface area from the adult activity of 100 MBq and the resulting radiation doses in normal children were compared with those that would have resulted from a schedule based on body weight.. The effective doses estimated by interpolation differed by up to 46% from those based on discrete phantoms and showed less variation. In children with normal bilateral renal function, the mean effective dose per administered activity was 0.91 +/- 0.08 mSv or 0.98 +/- 0.29 mSv by the two methods, respectively. Renal pathology reduced the effective dose, on average, by 15% of the value for normal patients.. Over the pediatric age range, the uniformity of effective dose values was improved by scaling the administered activity according to body surface area rather than to body weight.

Topics: Adolescent; Body Surface Area; Body Weight; Case-Control Studies; Child; Child, Preschool; Female; Humans; Infant; Kidney; Kidney Failure, Chronic; Male; Organotechnetium Compounds; Phantoms, Imaging; Radiation Dosage; Radiation Protection; Radionuclide Imaging; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid; Tissue Distribution

The aim of this study was to establish nomograms of renal length in children comparing age, body weight, and height. Renal lengths were obtained from data derived from Tc-99m DMSA scintigraphy in 266 patients with 532 kidneys that appeared normal on DMSA studies. The children's ages ranged from 6 days to 19 years. Renal length appeared to have nonlinear relationships with patient weight and age, but was found to correlate linearly with patient height. On average, scintigraphic renal length exceeded sonographic renal length by approximately 1 cm. The most likely explanation for this is the effect of respiration causing renal motion during the acquisition of the scintigraphic images. It is hoped that the nomograms derived from these data will be of use in routine clinical practice for nuclear medicine departments performing DMSA scintigraphy in children.

Topics: Aging; Body Height; Body Weight; Child; Female; Humans; Kidney; Male; Organotechnetium Compounds; Radionuclide Imaging; Reference Values; Sex Characteristics; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid

Meso-2,3-dimercaptosuccinic acid (DMSA) is a chelating agent used to treat heavy metal intoxication. DMSA has been reported to be teratogenic in the mouse, and it has been suggested that this teratogenicity may be secondary to DMSA-induced alterations in Zn metabolism. In the present study, 0, 400 or 800 mg DMSA/kg body weight were administered on gestation days 6-15 to pregnant Swiss mice by gavage (PO) or subcutaneous injection (SC). Mice were fed a diet containing 14 micrograms Zn, 10 micrograms Cu, 120 micrograms Fe, 1175 micrograms Mg and 6.8 mg Ca/g diet. A sub-group of mice in the 800 mg DMSA/kg SC group was fed a diet containing 250 micrograms Zn/g. DMSA administration did not result in overt maternal toxicity. There was no effect of the drug on fetal or placental weight, or on crown-rump length. However, some fetuses from DMSA-treated dams were characterized by skeletal abnormalities including supernumerary ribs, unossified anterior phalanges and malformed sternebrae. Drug exposure was not associated with consistent changes in tissue Zn, Fe, Ca or Mg levels. Supplemental Zn had no marked effects on the fetus. Fetal liver Cu concentrations exhibited dose-dependent decreases with increasing DMSA dose. This finding suggests that the developmental toxicity of DMSA may be mediated through disturbed maternal/fetal copper metabolism.

Topics: Animals; Body Weight; Copper; Female; Fetus; Intestinal Mucosa; Kidney; Liver; Mice; Minerals; Organ Size; Placenta; Pregnancy; Succimer; Zinc

1 The standard drug for the treatment of arsenic poisoning is BAL (dimercaprol). BAL possesses marked side-effects and a low safety ratio, drawbacks which new BAL analogues, DMPS and DMSA, do not possess. 2 The efficacy of three chelating agents, BAL, DMPS and DMSA, has been evaluated as a treatment for systemic organic arsenic poisoning, induced by intravenous dichloro(2-chlorovinyl)arsine (lewisite) administration to rabbits. Equimolar dosing schedules were used based upon realistic doses for the most toxic agent, BAL. 3 It was concluded that all three dimercapto chelating agents provided significant protection against the lethal systemic effects of lewisite, and, under the test conditions reported here, there was no significant difference between them in therapeutic efficacy. 4 The cause of mortality following intravenous lewisite in treated and untreated rabbits was pulmonary damage. 5 It is considered that DMPS and DMSA are worthy of further study as replacements for BAL in the treatment of systemic poisoning by lewisite.

Topics: Animals; Arsenic; Arsenic Poisoning; Arsenicals; Body Weight; Chelating Agents; Dimercaprol; Gallbladder; Lethal Dose 50; Liver; Lung; Male; Rats; Succimer; Unithiol

The present study was conducted to evaluate the effects of meso-2,3-dimercaptosuccinic acid (DMSA) on late gestation and postnatal viability and growth in the mouse. DMSA was given po to four groups of pregnant Swiss mice at 0, 200, 400, and 800 mg/kg/day from day 14 of pregnancy until postnatal day 21. At birth, the following data were recorded: length of gestation, number of live, dead, and abnormal pups, sex, and individual pup weights. Each pup was weighed again on day 4, 14, and 21 of lactation. Pinna detachment, incisor eruption and eye opening were also monitored. No treatment-related signs of toxicity were noted in any of the dams during the study. No adverse effects on offspring survival or development were evident in the 200 or 400 mg DMSA/kg/day groups. However, on days 14 and 21 of lactation a significant decrease in pup body weight was observed in the 800 mg/kg/day group. Also, a significant increase in the relative weight of the brain was seen in this group. The "no observable effect level" (NOEL) for health hazards to the developing pup was greater than 400 mg/kg/day. This dose is higher than the amounts of DMSA usually given in the treatment of human heavy metal intoxications.

Topics: Administration, Oral; Animals; Body Weight; Dose-Response Relationship, Drug; Female; Fetus; Growth; Mice; Organ Size; Pregnancy; Succimer

The conditioned flavor-aversion paradigm was used to assess the toxicity of acutely administered cadmium and the interaction of cadmium with the heavy-metal chelating agents dimercaprol (BAL) and dimercaptosuccinic acid (DMSA). Shortly after consuming saccharin, rats received ip administration of cadmium either alone or in combination with sc administration of BAL or DMSA. Three days later they were given the choice between consuming saccharin or water, and saccharin preferences were recorded. When compared to rats receiving either nothing or the vehicle, rats receiving cadmium displayed significant reductions in saccharin preference (i.e., conditioned flavor aversions). BAL and DMSA were also capable of producing conditioned flavor aversions when given alone. Rats receiving cadmium in combination with either BAL or DMSA displayed significant, but not complete attenuations of conditioned flavor aversions when compared to the flavor aversions of rats receiving cadmium alone. Chelator-induced blockade of cadmium-induced flavor-aversion conditioning was not obtained when BAL or DMSA administration was delayed by 4 hr. Attenuation of cadmium-induced aversions by BAL and DMSA extends earlier findings of an attenuation of lead-induced flavor-aversion conditioning by these complexing agents, and thus demonstrates further the utility of the flavor-aversion conditioning paradigm in characterizing metal-chelator interactions.

Topics: Animals; Behavior, Animal; Body Weight; Cadmium Poisoning; Chelating Agents; Conditioning, Operant; Dimercaprol; Dose-Response Relationship, Drug; Male; Rats; Succimer; Taste; Time Factors

meso-2,3-Dimercaptosuccinic acid (DMSA) is a water-soluble effective antidote for the treatment of heavy-metal intoxications. Information concerning the developmental toxicity of DMSA, however, has not been available. In order to determine the potential developmental toxicity of DMSA, pregnant Swiss mice were given 0, 410, 820, or 1640 mg DMSA/kg/day subcutaneously on Days 6-15 of gestation. Maternal effects included a significant reduction in weight gain during the exposure and postexposure periods at 1640 mg/kg/day. Food consumption was similar to controls at all doses levels except for the high dose group in the post-treatment period. Results of hematological and serum biochemical analyses in the DMSA-treated groups were comparable to those of the controls. However, in light of the pronounced effects on maternal weight gain the dose of 1640 mg/kg/day would be maternally toxic. Significant increases in the number of resorptions and the incidence of stunting were found, along with a significant decrease in the number of live fetuses per litter, when the 1640 mg/kg/day group was compared with the controls. Significant reductions in fetal body weight and fetal body length means were also found when the 820 and 1640 mg/kg/day groups were compared with the controls. Consequently, these results indicate that DMSA would be embryo-toxic to mice at 1640 mg/kg/day and fetotoxic at 820 mg/kg/day. In contrast, very slight fetotoxicity was observed at 410 mg/kg/day. Gross external, internal soft tissue, and skeletal examinations of the fetuses revealed that DMSA was teratogenic in the mouse when given subcutaneously at 820 and 1640 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Cell Count; Blood Chemical Analysis; Body Weight; Bone and Bones; Connective Tissue; Female; Mice; Organ Size; Pregnancy; Succimer; Sulfhydryl Compounds; Teratogens

Topics: Animals; Body Burden; Body Weight; Cerebellum; Kidney; Male; Mercury Radioisotopes; Methylmercury Compounds; Rats; Succimer; Sulfhydryl Compounds; Time Factors

Habu venom (HV) incubated with dimercaptosuccinic acid (DMS) or thiosuccinic acid (TMA), was given subcutaneously to mice. The LD50 of HV was 19.7 mg/kg, and after treatment with TMA and DMS, it was 38.1 and 47.1 mg/kg, respectively. The logarithm concentration--mortality curve for the DMS-treated HV shifted to the right compared with the curve for crude HV. The curve for the TMA-treated HV was intermediate between these two. Decimal two mg of HV was then incubated with DMS, and such was given intramuscularly to mice. Hemorrhage and edema which occurred after administration of crude HV were markedly decreased with injection of DMS-treated HV, but the myonecrosis was not greatly affected. At 24 hr after the intramuscular dosing of 1 mg of HV into rats, lymphopenia, acute involution of lymphatic tissue, decrease in liver glycogen and lipid granules in zona fasiculata were apparent, indicating the mark of a stressor. When the DMS-treated venom was administered, the blood picture and histological findings did not differ greatly from the controls. As DMS has marked anti-HV activity, it may be used to investigate treatments for cases of Habu snake bite.

Topics: Adrenal Cortex; Animals; Body Weight; Lethal Dose 50; Liver; Male; Mice; Organ Size; Rats; Snake Venoms; Succimer; Succinates; Sulfhydryl Compounds