Therapeutic Efficacy of a Few Diesters of Meso 2,3‐Dimercaptosuccinic Acid during Sub‐Chronic Arsenic Intoxication in Rats

Abstract

Therapeutic Efficacy of a Few Diesters of Meso 2,3-DimercaptosuccinicAcid during SubChronic Arsenic Intoxication in Rats: S.J.S. FLORA, et al. Division of Pharmacology and Toxicology, Defence Research and Development Establishment-The therapeutic efficacy of four diesters derivatives of meso 2,3-dimercaptosuccinic acid (DMSA) was investigated in subchronic arsenic intoxication in rats. Dimethyl DMSA (DMDMSA), diethyl DMSA (DEDMSA), diisopropyl DMSA (DiPDMSA) and diisoamyl DMSA (DiADMSA) were the diesters of DMSA with methyl, ethyl, isopropyl and isoamyl alcohols and were administered for two 5 day courses of treatment in male rats pre-exposed to 100 ppm arsenic (III) for 8 weeks. The results show that treatment with these diesters was effective in decreasing blood and soft tissue arsenic contents but was only moderately effective in recovering biochemical indicators. The results suggest that these diesters could be effective arsenic chelators but may be inferior to DMSA in recovering biochemical/ clinical indicators following sub-chronic arsenic exposure.

The ameliorative effects of DMSA and some vitamins against toxicity induced by lead in the testes of albino rats. II

“…Lead, in particular, can accumulate in the reproductive system and has been implicated in the development of oxidative stress via reactive oxygen species (ROS) and lipid peroxidation (Vaziri and Sica, 2004;Marchlewicz et al, 2004;Mishra and Acharya, 2004). In view of this, many investigators have used a variety of antioxidants and chelating agents for lead, including vitamin C (Hsu et al, 1998a;Saad and El-Sayed, 2014), vitamin E (Patra et al, 2011) and DMSA (Flora et al, 1997;Malvezzi et al, 2001) to prevent the occurrence and subdue oxidative stress in tissue. It has been reported that supplementation of vitamin E and/or C reduced sperm ROS generation, prevented loss of sperm motility and oocyte penetration capacity in lead-exposed rats (Hsu et al, 1998b;El-Neweshy and El-Sayed, 2011).…”

“…Therefore, vitamin C and vitamin E function together to protect membrane lipids from damage (Frei, 1991). Animal studies suggested that DMSA is an effective chelator of lead in soft tissues but it is unable to chelate lead from bone (Flora et al, 1997(Flora et al, , 2008. Vitamin C and/or vitamin E alone, or both in combination with conventional chelator was found to decrease lipid peroxide levels of soft organs (Patra et al, 2001).…”

Haematological, hepatic and renal alterations after repeated oral and intraperitoneal administration of monoisoamyl DMSA. II. Changes in female rats

“…Recently, some monoesters and diesters of DMSA have been developed and tried as therapeutic agents for metal poisoning in mice and rats (Kostial et al, 1995;Xu et al, 1995;Blanusa et al, 1997;Flora et al, 1997;Pande et al, 2001). The efficiency increased with the number of carbon atoms in the alkyl group of the DMSA monoester and the best results were obtained with monoisoamyl DMSA (MiADMSA) (Kostial et al, 1994), which has the ability to gain intracellular access via a probenecidsensitive and sulphinpyrazone-sensitive transport mechanism(s) (Tasende et al, 1992).…”

Protective effects of Selenium and/or Melatonin against Cadmium Chloride induced Chromosomal aberrations in Swiss Albino mice Mus musculus BALB/c

“…The efficacy of melatonin in cadmium induced cytotoxicity is mainly attributed to its high lipophilicity (Reiter, 2000). It is well documented that the lipophilic agents are found to be very effective in reducing toxic effects of heavy metals and their elimination from various organ systems (Flora et al, 1997;ElSokkary et al;2005). Due to its small size and lipophilicity, melatonin crosses biological membranes easily, thus reaching all compartments of the cell.…”