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Dimercaptosuccinic acid
About: Dimercaptosuccinic acid is a research topic. Over the lifetime, 482 publications have been published within this topic receiving 10548 citations. The topic is also known as: Chemet & Meso-dimercaptosuccinic acid.
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TL;DR: The possibility that combined administration of N‐acetylcysteine (NAC) and meso 2,3‐dimercaptosuccinic acid (DMSA) was capable of achieving better reversibility in the parameters indicative of arsenic‐induced oxidative stress than individual treatment with either of these drugs was explored.
Abstract: 1. The present study examined whether arsenic induces oxidative stress in liver, brain and erythrocytes (RBC) based on the investigation of certain selected parameters. It also explored the possibility that combined administration of N-acetylcysteine (NAC) and meso 2,3-dimercaptosuccinic acid (DMSA) was capable of achieving better reversibility in the parameters indicative of arsenic-induced oxidative stress than individual treatment with either of these drugs. 2. Male rats were exposed to 100 p.p.m. sodium arsenite in their drinking water for 12 weeks (equivalent to 12 mg/kg As). The arsenic was then removed and rats were given NAC (1 mmol/kg per day), DMSA (1 mmol/kg per day) or a combination of the two, orally, once daily for 5 days. Animals not given arsenic and those given arsenic but not NAC or DMSA served as negative and positive controls, respectively. 3. Twelve weeks of arsenic exposure was found to deplete glutathione (GSH) levels, increase oxidized glutathione (GSSG) and promote malondialdehyde (MDA) production in both liver and brain samples. In addition to a significant reduction in RBC delta-aminolevulinic acid dehydratase (ALAD) activity and GSH levels, a marked elevation in MDA production may also contribute to arsenic-induced oxidative stress. 4. Treatment with either NAC or DMSA alone partially reversed arsenic-induced alterations in hepatic GSH and MDA, while only brain MDA levels responded favourably to these drugs. Only DMSA appeared to restore blood ALAD, while RBC MDA levels responded favourably to both drugs. Treatment with DMSA also produced an effective depletion of blood and hepatic arsenic concentrations. In the liver, most of these parameters were more effectively reversed by combined treatment with NAC and DMSA compared with the effects of either drug alone. 5. These results provide in vivo evidence of arsenic-induced oxidative stress in liver, brain and RBC and indicate that these effects can be mitigated by pharmacological intervention that encompasses combined treatment with NAC and DMSA.
286 citations
TL;DR: It is concluded that acquired renal scarring only occurs at sites corresponding to previous areas of acute pyelonephritis, the acute parenchymal inflammatory changes of acute Pyel onephritis are reversible and do not lead to new renal Scarring in the majority of cases, and once acute pyELonephitis has occurred ultimate renal scarred is independent of the presence or absence of vesicoureteral reflux.
278 citations
TL;DR: It is found that cortical scintigraphy is more sensitive than ultrasonography in detecting renal changes, and it is believed that it should be added to the initial examination of children with suspected pyelonephritis.
249 citations
TL;DR: It is found that acquired renal scarring only occurs in sites corresponding exactly to previous areas of acute pyelonephritis demonstrated by DMSA scintigraphy at the time of infection, providing convincing evidence that renal parenchymal infection, rather than vesicoureteral reflux, is the prerequisite for acquired (postnatal) renal Scarring.
210 citations
TL;DR: Preclinical and clinical evidence now indicate that meso-2,3-dimercaptosuccinic acid, an Orphan Drug, shows the most promise for being effective in this regard, and has an extracellular distribution that may be responsible for its low toxicity compared to other dithiols.
Abstract: The primary purpose of this article is to summarize the recent investigations dealing with the pharmacology and toxicology of meso-2,3-dimercaptosuccinic acid, an orally effective chelating agent. The need for a better chelating agent for treating young children and pregnant women with lead intoxication has been apparent for some time. Preclinical and clinical evidence now indicate that meso-2,3-dimercaptosuccinic acid, an Orphan Drug, shows the most promise for being effective in this regard. It has an extracellular distribution that may be responsible for its low toxicity compared to other dithiols. No attempt has been made to compare it in a rigorous and thorough manner with other chelating agents. That has not been the purpose of this review. The advantages of meso-DMSA, however, compared to CaNa2EDTA for the treatment of lead intoxication, have been outlined. Significant advances have been made recently in elucidating the structures of the metal chelates of DMSA. There is a striking difference between the structures of the lead chelate of meso-DMSA and those of racemic-DMSA. The former chelates by coordination of one sulfur and one oxygen atom with Pb. The latter can form chelates via the two sulfur atoms or via one oxygen and one sulfur atom. Solubility of the lead chelates depends on the ionization of the noncoordinated thiol and carboxylic acid groups. Bimane derivatization, HPLC, and fluorescence, as well as gas chromatography can be used for analysis of DMSA in biological fluids. The acid dissociation constants for meso- and racemic-DMSA have been summarized from the literature as have the formation constants of some of the DMSA chelates. DMSA is biotransformed to a mixed disulfide in humans. By 14 hr after DMSA administration (10 mg/kg), only 2.5% of the administered DMSA is excreted in the urine as unaltered DMSA and 18.1% of the dose is found in the urine as altered forms of DMSA. Most altered DMSA in the urine is in the form of a mixed disulfide. It consists of DMSA in disulfide linkages with two molecules of L-cysteine. One molecule of cysteine is attached to each of the sulfur atoms of DMSA. The remaining 10% of the altered DMSA was in the form of cyclic disulfides of DMSA. So far, the mixed disulfide has been found in human but not in rabbit, mouse, or rat urine. Apparently there are species differences in how organisms metabolize meso-DMSA.(ABSTRACT TRUNCATED AT 400 WORDS)
190 citations