Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Succimer”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources
PubMed2004

Therapeutic efficacy of lipoic acid in combination with dimercaptosuccinic acid against lead-induced renal tubular defects and on isolated brush-border enzyme activities.

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.

5-Aminolevulinate Synthetase↗
PubMed2006

Cadmium inhibits delta-aminolevulinate dehydratase from rat lung in vitro: interaction with chelating and antioxidant agents.

The effect of cadmium (Cd(2+)) on delta-aminolevulinate dehydratase (delta-ALA-D) activity from rat lung in vitro was investigated. delta-ALA-D activity, a parameter for metal intoxication, has been reported as a target of Cd(2+) in different tissues. The protective effect of monotherapies with dithiol chelating (meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS)) or antioxidant agents (ascorbic acid, diphenyl diselenide (PhSe)(2), and N-acetylcysteine (NAC)) was evaluated. The effect of a combined therapy (dithiol chelatingxantioxidant agent) was also studied. Zinc chloride (ZnCl(2)) and dithiothreitol (DTT) were used to investigate the mechanisms involved in cadmium, chelating and antioxidant effects on delta-ALA-D activity. Cadmium inhibited rat lung delta-ALA-D activity at low concentrations. DTT (3mM), but not ZnCl(2) (100microM), protected the inhibition of enzyme activity caused by Cd(2+). Chelating agents were not effective in restoring the enzyme activity. DMPS and DMSA presented inhibitory effect on enzyme activity. DTT restored the inhibition caused by both chelating agents, but ZnCl(2) restored only the inhibitory effect induced by DMSA. These compounds caused a marked potentiation of delta-ALA-D inhibition induced by Cd(2+). ZnCl(2) did not restore inhibition of enzyme activity caused by Cd(2+) plus chelating agents. Conversely, DTT restored the inhibition induced by Cd(2+)/DMSA, but not by Cd(2+)/DMPS. Antioxidants were not effective in ameliorating delta-ALA-D inhibition induced by Cd(2+), whereas ascorbic acid potentiated the enzyme inhibition induced by this metal. A combined effect of Cd(2+)xDMPSx(PhSe)(2) and Cd(2+)xDMPSxNAC was observed. There was no combined effect of Cd(2+)xchelatorxantioxidants when DMSA was used. This study demonstrated that Cd(2+)inhibited delta-ALA-D activity and chelating and antioxidant agents, alone or combined, did not restore the enzyme activity. In contrast, these compounds potentiated the inhibition induced by Cd(2+) in rat lung.

Acetylcysteine↗
PubMed2006

Effects of combined administration of captopril and DMSA on arsenite induced oxidative stress and blood and tissue arsenic concentration in rats.

We compared the therapeutic efficacy of captopril and a thiol chelating agent, meso 2,3-dimercaptosuccinic acid (DMSA) either individually or in combination against arsenite induced oxidative stress and mobilization of metal in rats. Animals were exposed to 100 ppm arsenite as sodium arsenite in drinking water for six weeks followed by treatment with DMSA (50 mg/kg, orally), captopril (50 mg/kg, intraperitoneally) either alone or in combination, once daily for 5 consecutive days. Arsenite exposure led to a significant depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity, glutathione and platelet levels while significantly increased the level of reactive oxygen species (in RBCs). Hepatic reduced glutathione (GSH) level showed a significant decrease while, thiobarbituric acid reactive substances (TBARS) levels increased on arsenite exposure indicating arsenite induced hepatic oxidative stress. Kidney GSH, GSSG, catalase and TBARS remained unchanged on arsenite exposure. Treatment with DMSA was effective in increasing ALAD activity while, captopril was ineffective when given alone. Captopril when co-administered with DMSA also provided no additional beneficial effect on blood ALAD activity but significant brought altered platelet counts back to the normal value. In contrast, administration of captopril alone provided significant beneficial effects on hepatic oxidative stress, and in combination with DMSA provided a more pronounced recovery in the TBARS level compared to the individual effect of DMSA and captopril. Renal biochemical variables remained insensitive to arsenite and any of the treatments. Interestingly, combined administration of captopril with DMSA had a remarkable effect in depleting total arsenic concentration from blood and soft tissues. These results lead us to conclude that captopril administration during chelation treatment had some beneficial effects particularly on the protection of inhibited blood ALAD activity, and depletion of arsenic level. The study supports our earlier conclusion that a co-administration of an antioxidant is more beneficial than monotherapy with the chelating agents, in order to achieve optimal effects of chelation in arsenite toxicity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Involvement of lipid peroxidation and organic peroxides in UVA-induced matrix metalloproteinase-1 expression.

Ultraviolet A (UVA) irradiation causes human skin aging and skin cancer at least partially through the activation of matrix metalloproteinases (MMPs). MMP-1, the interstitial collagenase, is responsible for the degradation of collagen and is involved in tumor progression in human skin. The present study uses human skin fibroblast cells (FEK4) to investigate the involvement of lipid peroxidation and the role of peroxides as possible mediators in MMP-1 activation by UVA. Preincubation with the antioxidants butylated hydroxytoluene and Trolox reduced UVA-dependent MMP-1 upregulation, suggesting that peroxidation of membrane lipids is involved. Blocking the iron-driven generation of lipid peroxides and hydroxyl radicals by different iron chelators led to a decrease in UVA-induced MMP-1 mRNA accumulation. Moreover, modulation of glutathione peroxidase activity by use of the specific inhibitor mercaptosuccinate (MS) or by the depletion of glutathione (using buthionine-S, R-sulfoximine, BSO), enhanced the UVA-dependent MMP-1 response. Finally, UVA irradiation generated a significant increase in intracellular peroxide levels which is augmented by pretreatment of the cells with BSO or MS. Our results demonstrate that lipid peroxidation and the production of peroxides are important events in the signalling pathway of MMP-1 activation by UVA.

Antioxidants↗
PubMed2004

The effects of meso-2,3-dimercaptosuccinic acid and oligomeric procyanidins on acute lead neurotoxicity in rat hippocampus.

Oxidative stress is considered to be a mechanism involved in lead neurotoxicity. Apoptosis is also thought to relate to lead neurotoxicity. The present study, focused on the hippocampus, was designed to investigate the two possible mechanisms involved in lead neurotoxicity and the potential protective effects of 2,3-dimercaptosuccinic acid (DMSA) and oligomeric procyanidins (OPC). It was proved that reactive oxygen species and oxidative damage were implicated in the induction of apoptosis induced by lead in the hippocampus. Administration of DMSA attenuated the oxidative stress and apoptosis in addition to having strong chelating and lead-removing capacity. OPC alone had antioxidant protective effects in the hippocampus but no removing capacity for lead in vivo despite showing higher affinity and stronger chelating ability for Pb(2+) than DMSA in vitro. It is suggested that OPC chelates Pb(2+) but does not discharge it from the body and even accumulates Pb(2+) in some organs. At the same time, a reasonable deduction can also be made that the complex of OPC-Pb(2+) prevents or at least weakens the neurotoxicity of Pb(2+). Whether this complex displays toxicity over a long time span should be studied further.

Animals↗
PubMed2004

Combined efficacies of lipoic acid and 2,3-dimercaptosuccinic acid against lead-induced lipid peroxidation in rat liver.

Oxidative stress with subsequent lipid peroxidation has been postulated as one mechanism for lead toxicity. Hence in assessing the protective effects of lipoic acid (LA) and meso 2,3-dimercaptosuccinic acid (DMSA) on lead toxicity, they were tested either separately or in combination for their effects on selected indices of hepatic oxidative stress. Elevated levels of lipid peroxides were accompanied by altered antioxidant defense systems. Lead acetate (Pb - 0.2%) was administered in drinking water for five weeks to induce toxicity. LA (25 mg kg(-1) body wt. day(-1) i.p) and DMSA (20 mg kg(-1) body wt. day(-1) i.p) were administered individually and also in combination during the sixth week. Lead damage to the liver was evident in the decreases in hepatic enzymes alanine transaminase (-38%), aspartate transaminase (-42%) and alkaline phosphatase (-43%); increases in lipid peroxidation (+38%); decreases in the antioxidant enzymes catalase (-45%), superoxide dismutase (-40%), glutathione peroxidase (-46%) and decreases in glutathione (-43%) and decreases in glutathione metabolizing enzymes, glutathione reductase (-59%), glucose-6-phosphate dehydrogenase (-27%) and glutathione-S-transferase (-42%). In combination LA and DMSA completely ameliorated the lead induced oxidative damage. Either compound alone was however only partially protective against lead damage.

Alanine Transaminase↗
PubMed2007

Does a normal DMSA obviate the performance of voiding cystourethrography in evaluation of young children after their first urinary tract infection?

OBJECTIVE: To determine whether a normal technetium-99m-labeled dimercaptosuccinic acid (DMSA) renal scan obviates the need for voiding cystourethrography (VCUG) in evaluating young children after their first urinary tract infection (UTI). STUDY DESIGN: This was a 10-year retrospective review of 142 children (age < or = 2 years, 77 boys and 65 girls) who had their first UTI and were admitted to a tertiary care general hospital. The association between DMSA renal scan results and VCUG results performed 48 hours and 1 month after diagnosis was evaluated. RESULTS: DMSA renal scans and VCUG were performed in 142 patients. Of these, 99 patients (69.7%) had evidence of pyelonephritis, although only 2 (1.4%) had evidence of renal scarring; 42 (29.6%) had vesicoureteral reflux (VUR) on VCUG. The sensitivity, specificity, positive and negative predictive values, and likelihood ratio negative for abnormalities on DMSA renal scans for detecting the the presence of VUR on VCUG were 88% (95% confidence interval [CI] = 73% to 100%), 36% (95% CI = 26% to 46%), 37% (95% CI = 27% to 46%), 88 % (95% CI = 73% to 100%), and 0.33 (95% CI = 0 to 0.88), respectively. CONCLUSIONS: Children with a negative DMSA renal scan during their first UTI episode rarely have VUR and may never have high-grade VUR. Avoiding VCUGs in children with negative DMSA renal scans could significantly reduce the use of this potentially traumatic test.

Child, Preschool↗
PubMed2005

Arsenic induced blood and brain oxidative stress and its response to some thiol chelators in rats.

Chronic arsenic toxicity is a widespread problem, not only in India and Bangladesh but also in various other regions of the world. Exposure to arsenic may occur from natural or industrial sources. The treatment that is in use at present employs administration of thiol chelators, such as meso 2,3-dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), which facilitate its excretion from the body. However, these chelating agents are compromised with number of limitations due to their lipophobic nature, particularly for their use in cases of chronic poisoning. During chronic exposure, arsenic gains access into the cell and it becomes mandatory for a drug to cross cell membrane to chelate intracellular arsenic. To address this problem, analogs of DMSA having lipophilic character, were examined against chronic arsenic poisoning in experimental animals. In the present study, therapeutic efficacy of meso 2,3-dimercaptosuccinic acid (DMSA), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), monoisoamyl DMSA (MiADMSA) were compared in terms of reducing arsenic burden, as well as recovery in the altered biochemical variables particularly suggestive of oxidative stress. Adult male Wistar rats were given 100-ppm arsenic for 10 weeks followed by chelation therapy with the above chelating agents at a dose of 50 mg/Kg (orally) once daily for 5 consecutive days. Arsenic exposure resulted in marked elevation in reactive oxygen species (ROS) in blood, inhibition of ALAD activity and depletion of GSH. These changes were accompanied by significant decline in blood hemoglobin level. MiADMSA was the most effective chelator in reducing ROS in red blood cells, and in restoring blood ALAD compared to two other chelators. Brain superoxide dismutase (SOD) and glutathione peroxidase (GPx) decreased, while ROS and TBARS increased significantly following arsenic exposure. There was a significant increase in the activity of glutathione-S-transferase (GST) with a corresponding decline in its substrate i.e. glutathione. Among all the three chelators, MiADMSA showed maximum reduction in the level of ROS in brain. Additionally, administration of MiADMSA was most effective in counteracting arsenic induced inhibition in brain ALAD, SOD and GPx activity. Based on these results and in particular higher metal decorporation from blood and brain, we suggest MiADMSA to be a potential drug of choice for the treatment of chronic arsenic poisoning. However, further studies are required for the choice of appropriate dose, duration of treatment and possible effects on other major organs.

5-Aminolevulinate Synthetase↗
PubMed2005

Monoisoamyl dimercaptosuccinic acid induced changes in pregnant female rats during late gestation and lactation.

Monoisoamyl dimercaptosuccinic acid (MiADMSA), a vicinal thiol chelating agent and an analogue of a conventional metal chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA) has recently been gaining recognition to be more effective chelating agent than DMSA in mobilizing lead, mercury and arsenic. However, very little information is available on the toxicological properties of this chelator. In the present study, MiADMSA was administered to pregnant female rats from day 14 of gestation to day 21 of lactation at different doses through oral (p.o.) and intraperitoneal (i.p.) routes to examine the toxicity in the pups and dams. Results suggested that MiADMSA had no effect on period of gestation, litter-size, sex ratio, and viability and lactation. No skeletal defects were observed following the administration of the chelator. However, MiADMSA administration produced few signs of oxidative stress in dams particularly at the higher doses (100 and 200mg/kg) as evident from increased thiobarbituric acid reactive substances (TBARS) in RBCs and decrease in the delta-aminolevulinic acid dehydratase (ALAD) activity. Administration of MiADMSA also caused some alterations in the essential metal concentration in the soft tissues especially tissue copper loss in lactating mothers and pups, which would be of some concern. Apart from copper, changes were also observed in the tissue zinc concentrations in mothers and pups following MiADMSA administration. The study thus suggests that the chelator is relatively safe during late gestation and it does not cause any major alteration in the mothers and the developing pups. However, detailed studies with MiADMSA, post-toxic metal exposure in pregnant animals may provide useful information.

Animals↗
PubMed2006

Porphyrinuria in childhood autistic disorder: implications for environmental toxicity.

To address a possible environmental contribution to autism, we carried out a retrospective study on urinary porphyrin levels, a biomarker of environmental toxicity, in 269 children with neurodevelopmental and related disorders referred to a Paris clinic (2002-2004), including 106 with autistic disorder. Urinary porphyrin levels determined by high-performance liquid chromatography were compared between diagnostic groups including internal and external control groups. Coproporphyrin levels were elevated in children with autistic disorder relative to control groups. Elevation was maintained on normalization for age or to a control heme pathway metabolite (uroporphyrin) in the same samples. The elevation was significant (P < 0.001). Porphyrin levels were unchanged in Asperger's disorder, distinguishing it from autistic disorder. The atypical molecule precoproporphyrin, a specific indicator of heavy metal toxicity, was also elevated in autistic disorder (P < 0.001) but not significantly in Asperger's. A subgroup with autistic disorder was treated with oral dimercaptosuccinic acid (DMSA) with a view to heavy metal removal. Following DMSA there was a significant (P = 0.002) drop in urinary porphyrin excretion. These data implicate environmental toxicity in childhood autistic disorder.

Administration, Oral↗
PubMed2005

2,3-Dimercaptopropanol, 2,3-dimercaptopropane-1-sulfonic acid and meso-2,3-dimercaptosuccinic acid increase lead-induced inhibition of delta-aminolevulinate dehydratase in vitro and ex vivo.

We investigated the effects of dimercaprol (BAL), meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-1-propanesulphonic acid (DMPS) on human blood delta-aminolevulinate dehydratase (delta-ALA-D) activity, the most reliable indicator of lead intoxication in humans, in the presence of lead in vitro. Furthermore, we studied the effects of the chelating agents, administered subcutaneously, on delta-ALA-D activity in blood and tissues of mice submitted to sub-acute lead exposure (50 mg/kg for 15 consecutive days, subcutaneously). In vitro results demonstrated that human blood delta-ALA-D activity was significantly inhibited (62%) by lead acetate. Lead acetate (1-1000 microM) pre-incubated with human blood increased the inhibitory potency of this compound on delta-ALA-D when compared to the assay without pre-incubation (89%). Chelating agents caused a marked potentiation of delta-ALA-D inhibition induced by lead, in vitro. One of the most notable observations in the present study was the correspondence between in vitro and ex vivo effects. In fact, BAL and DMPS increase the inhibitory effect of lead on delta-ALA-D activity from mice blood. The complexes formed (lead and chelators) were more inhibitory than lead alone in kidney and liver enzyme activity, ex vivo.

Animals↗
PubMed2004

Therapeutic potential of monoisoamyl and monomethyl esters of meso 2,3-dimercaptosuccinic acid in gallium arsenide intoxicated rats.

The dose dependent effects of monoisoamyl and monomethyl esters of meso 2,3-dimercaptosuccinic acid (DMSA) (0.1, 0.3 and 0.5 mmol kg(-1), intraperitoneally (i.p.) once daily for 5 days) to offset the characteristic biochemical, immunological, oxidative stress consequences and DNA damage (based on DNA fragmentation and comet assay) following sub-chronic administration of gallium arsenide and the mobilization of gallium and arsenic were examined. The effects of these chelators alone in normal animals too were examined on above-mentioned variables. Male Wistar rats were exposed to 10 mg kg(-1), GaAs, orally once daily for 12 weeks and were administered DMSA or two of its monoesters (monoisoamyl or monomethyl) for 5 consecutive days. DMSA was used as a positive control. DMSA and its derivatives, when given alone, generally have no adverse effects on various parameters. After 5 days of chelation therapy in GaAs pre-exposed rats, MiADMSA was most effective in the reduction of inhibited blood delta-aminolevulinic acid dehydratase (ALAD) activity and zinc protoporphyrin level while, all three chelators effectively reduced urinary ALA excretion, compared to GaAs alone exposed rats. MiADMSA was also effective, particularly at a dose of 0.3 mmol kg(-1), in enhancing the inhibited hepatic transaminase activities. Parameters indicative of oxidative stress responded less favorably to the chelation therapy, however, three chelators significantly restored the altered immunological variables. MiADMSA was relatively more effective than the other two chelators. GaAs produced significant DNA damage in the liver and kidneys and the chelation treatment had moderate but significant influence in reducing DNA damage. All three chelators significantly reduced arsenic concentration and, however, MiADMSA was more effective than the other two chelators in depleting arsenic concentration from blood and other soft tissues. A dose of 0.3 mmol kg(-1) was found to be relatively better than the other two doses examined. Gallium contents of blood and soft tissues remained uninfluenced by the chelation therapy. Significant loss of copper after MiADMSA administration, however, is of concern and requires further exploration. Additionally, further studies are required for the choice of appropriate dose, duration of treatment and possible toxic/side effects. Keeping in view the promising role of MiADMSA in the treatment of GaAs poisoning, these data will be needed for the registration of this chelating agent as licensed drug for the treatment of gallium arsenide intoxication.

Aminolevulinic Acid↗
PubMed2005

Beneficial role of monoesters of meso-2,3-dimercaptosuccinic acid in the mobilization of lead and recovery of tissue oxidative injury in rats.

We investigated the therapeutic efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) and two of its analogues, monomethyl dimercaptosuccinic acid (MmDMSA) and mono-cyclohexyl dimercaptosuccinic acid (MchDMSA) in reducing lead concentration in blood and soft tissues, and in recovering lead induced oxidative stress in rats. Male wistar rats were exposed to lead acetate in drinking water for 20 weeks, followed by 5 days of oral treatment with DMSA (100mg/kg, oral, once daily), MmDMSA or MchDMSA (50 and 100mg/kg). Biochemical variables indicative of oxidative stress along with lead, zinc and copper concentration were evaluated in blood and other soft tissues. Exposure to lead caused a significant decrease in blood delta-aminolevulinic acid dehydratase (ALAD) activity and glutathione (GSH) level. These changes were accompanied by inhibition of kidney ALAD and an increase in delta-aminolevulinic acid synthatase (ALAS) activity in liver and kidneys. Also seen were a pronounced depletion of brain GSH, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and decreased superoxide dismutase (SOD) activity and an increase in thiobarbituric acid reactive substances (TBARS) and reactive oxygen species (ROS) levels. These biochemical changes were correlated with an increased uptake of lead in blood and soft tissues. Blood and kidneys zinc concentration decreased significantly following lead exposure while, copper concentration remained unchanged. No effect of chelation on hepatic zinc concentration was noted, only liver copper concentration showed significant depletion on treatment with DMSA and MmDMSA (100mg/kg). Treatment with DMSA, MmDMSA and MchDMSA provided significant recovery in altered biochemical variables and brain DNA damage besides significant depletion of tissue lead burden. Among the chelating agents used, MchDMSA and MmDMSA provided better recovery in altered biochemical variables and depletion of lead concentration in tissues compared to DMSA. The above results suggest DMSA monoesters to be a better treatment option than DMSA in eliciting recovery to the altered biochemical variables and in the depletion of body lead burden.

Acetylcholinesterase↗
PubMed2006

Therapeutic effects of hypothermia on Lewisite toxicity.

The cytotoxicity of the arsenical vesicant Lewisite was assessed in first passage cultures of proliferating neonatal human skin keratinocytes. Both munitions grade and distilled Lewisite were extremely toxic with LC(50) values in the low ng/ml range, with no significant differences between them. This similarity in toxicity was also mirrored with respect to their toxic effects on hairless guinea pig skin. Two-, 4- and 6-min vapour exposures of these agents resulted in similar and severe skin injury that was obvious by 3-5h post-exposure and almost maximal at 24h. The toxicity of Lewisite in culture was temperature dependent, with a >10-fold reduction in 24h LC(50) values as the incubation temperature was reduced from 37 to 25 degrees C. However, this cooling induced protection was not persistent. In contrast, cooling of Lewisite exposed hairless guinea pig skin at approximately 10 degrees C for as little as 30 min post-exposure resulted in dramatic and permanent protection, with 4h of cooling almost completely eliminating Lewisite induced skin injury. Further, significant protection was also evident even when cooling was delayed for as long as 2h post-Lewisite exposure. In an effort to investigate whether cooling might also increase the window in which chelation therapy against this vesicant agent would be useful, we examined the protective effects of the heavy metal chelator dimercaptosuccinic acid (DMSA). Topical application to Lewisite exposed skin was extremely protective, even when delayed for 2h after Lewisite. Cooling of Lewisite exposed skin for 2h, followed by DMSA topical application resulted in decreased skin injury compared to either treatment in isolation. It appears that the simple and non-invasive application of cooling measures may provide not only significant therapeutic relief to Lewisite exposed skin, but that it may also increase the therapeutic window in which medical countermeasures against this vesicant agent are useful.

Animals↗
PubMed2005

Simultaneous administration of sodium selenite and mercuric chloride decreases efficacy of DMSA and DMPS in mercury elimination in rats.

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.

Animals↗
PubMed2005

Combined efficacies of DL-alpha-lipoic acid and meso 2,3 dimercaptosuccinic acid against arsenic induced toxicity in antioxidant systems of rats.

Health hazards caused by heavy metals have become a great concern to the population. Arsenic as an environmental agent is considered to be a toxic substance due to its carcinogenic potential in humans. Since arsenic compounds might exert their toxicity by the generation of reactive oxygen species, we have evaluated the effect of both DL-alpha-lipoic acid (LA) and meso 2,3 dimercapto succinic acid (DMSA) on the antioxidants and lipid peroxidation in arsenic treated rats. The objective of the study was to determine whether DL-alpha-lipoic acid and meso 2,3 dimercapto succinic acid could rehabitate antioxidant depletion and damage to biomolecules in protection against oxidative insults. A significant increase in the levels of reactive oxygen species formation and lipid peroxidation and decrease in the activities of antioxidant enzymes were observed in arsenic exposed rats. Supplementation of DL-alpha-lipoic acid and meso 2,3 dimercapto succinic acid to arsenic fed rats significantly increased the activities of superoxide dismutase, catalase, glutathione peroxidase with elevation in the levels of reduced glutathione, total sulfhydryl, ascorbic acid and alpha-tocopherol. In addition, significant decrease in the levels of reactive oxygen species formation and lipid peroxidation was also observed in our study. From our results, we conclude that DL-alpha-lipoic acid and meso 2,3 dimercapto succinic acid play a synergistic role in decreasing arsenic induced oxidative damage by elevating the antioxidant status in liver and kidney.

Animals↗
PubMed2006

Role of positional instillation of contrast cystography in the algorithm for evaluating children with confirmed pyelonephritis.

OBJECTIVES: To assess the utility of positional instillation of contrast (PIC) cystography in detecting vesicoureteral reflux (VUR) in patients with renal scarring from recurrent febrile urinary tract infections that standard voiding cystourethrography and nuclear cystogram imaging failed to reveal. METHODS: Between June 2004 and November 2004, a total of 5 pediatric patients with recurrent febrile urinary tract infections and radiologic evidence of upper tract involvement were examined with PIC cystography. All patients had at least one previous negative standard reflux study (voiding cystourethrography or nuclear cystography). RESULTS: All 5 patients showed VUR on PIC cystography. Unilateral reflux was detected in 3 patients, and 2 patients had bilateral VUR. CONCLUSIONS: The PIC cystogram should be integrated into the algorithm for diagnosing patients with recurrent febrile urinary tract infection, who do not exhibit VUR on standard imaging modalities. The morbidity associated with undiagnosed VUR, as demonstrated by this group of patients, suggests that permanent renal damage may be prevented by early diagnosis and treatment.

Absorbable Implants↗
PubMed2003

Studies of urinary cystine precipitation in vitro: ontogeny of cystine nephrolithiasis and identification of meso-2,3-dimercaptosuccinic acid as a potential therapy for cystinuria.

Children with fully recessive (Type I/I) cystinuria have a high risk of stone formation in the first decade of life. To assess the tendency for cystine to precipitate in individual urine samples, we developed an in vitro assay in which radiolabelled cystine (4mM) was dissolved in urine at 37 degrees C after alkalization to pH 10. Samples were then brought to pH 5, cooled, and centrifuged. The % decrease in supernatant cpm was used as a measure of cystine precipitation (CP). CP varied widely among normal children (74%+/-34) whereas variability of repeated determinations on a single adult individual was modest (64%+/-3.3). The assay was used to compare various potential therapies for cystinuria. Precipitation of exogenous cystine from normal urine was strongly inhibited by addition of D-penicillamine (CP: 8%+/-3) or dimercaptosuccinic acid (DMSA) (CP: 5%+/-1), at urinary concentrations attained by standard oral doses of each drug. Mercaptopropionylglycine (MPG) was moderately effective (CP: 43%+/-9), whereas captopril was a weak inhibitor (CP: 63%+/-12). Precipitation of endogenous cystine (2191 micromol/L) from a cystinuric patient showed that DMSA and D-penicillamine were again highly effective compared to the other agents. In addition DMSA and penicillamine added to the same patient's urine reduced the free cystine by 50% (as measured by automated amino acid analyzer) whereas MPG and captopril had no effect. In conclusion, DMSA is comparable to D-penicillamine as an in vitro inhibitor.

Adolescent↗