Mobilization of cadmium by liposome-encapsulated meso-2,3-dimercaptosuccinic acid in pre-exposed mice.

meso-2,3-Dimercaptosuccinic acid (DMSA) treatment in free of liposome-encapsulated form was given to mice pre-exposed to cadmium as CdCl2 (2 intraperitoneal injections; 0.5 mg Cd/kg along with 5 microCi 109CdCl2 in 4 ml volume within 24 h). Both treatments removed cadmium from liver, spleen, testis and blood with liposomal DMSA exhibiting higher efficacy in mobilizing cadmium not only from whole organs but also from liver proteins. It also resulted in higher excretion of cadmium via urine as compared with free DMSA or saline treatment. Whereas this treatment eliminated significantly higher amounts of cadmium via the fecal route throughout the period examined, free DMSA responded only 48 h after treatment and was less effective. The results suggest mobilization of cadmium from intracellular sites of deposition. However, DMSA in the dose administered (24 mumol/kg i.v.) in either form was ineffective in decorporating cadmium from the kidney, the critical organ in cadmium intoxication.

Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity.

Heavy metals are, unfortunately, present in the air, water, and food supply. Cases of severe acute lead, mercury, arsenic, and cadmium poisoning are rare; however, when they do occur an effective, non-toxic treatment is essential. In addition, chronic, low-level exposure to lead in the soil and in residues of lead-based paint, to mercury in the atmosphere, in dental amalgams and in seafood, and to cadmium and arsenic in the environment and in cigarette smoke is much more common than acute exposure. Meso-2,3-dimercaptosuccinic acid (DMSA) is a sulfhydryl-containing, water-soluble, non-toxic, orally-administered metal chelator which has been in use as an antidote to heavy metal toxicity since the 1950s. More recent clinical use and research substantiates this compound s efficacy and safety, and establishes it as the premier metal chelation compound, based on oral dosing, urinary excretion, and its safety characteristics compared to other chelating substances.

Influence of size of liposomes in potentiating the efficacy of encapsulated triethylenetetramine-hexaacetic acid (TTHA) against cadmium intoxication.

Polyaminocarboxylic acids have widely been used an antidotes in heavy metal intoxication, however their hydrophilic nature renders them to be mostly distributed extracellularly. To facilitate the intracellular delivery of such chelating agent, triethlenetetraamine-hexaacetic acid (TTHA) was encapsulated in small unilamellar vesicles (SUV) or dehydration rehydration vesicles (DRV) and its effect was examined in the amelioration of cadmium toxicity. Mice were administered cadmium (0.2 mg/kg B.wt.) as CdCl2 intraperitoneally daily for five days. After a period of four weeks rest. they were given two intravenous injections of TTHA as free material or encapsulated in liposomes (0.16 m mole/kg) at a gap of 48 hours. Urinary and fecal elimination of cadmium and its distribution in the liver, kidney and spleen was monitored after TTHA treatment. The results indicate the efficacy of TTHA in removing cadmium from the body organs of preexposed animals and its excretion through urine and feces was maximum when it was encapsulated in SUV liposomes.

Efficacy of liposome encapsulated triethylenetetraamine hexaacetic acid (TTHA) against cadmium intoxication: role of lipid composition.

Efficacy of Triethylenetetraamine hexaacetic acid (TTHA) encapsulated in liposomes having different lipid compositions was examined in animals pre-exposed to cadmium. Mice were injected with cadmium as cadmium (II) chloride 0.5 mg/kg b. wt. intraperitoneally daily for five days. Four weeks after the last injection of cadmium they were administered three injections of TTHA encapsulated in liposomes composed of either phosphatidyl choline:cholesterol (PC:Chol) or sphingomyelin:cholesterol (SM:Chol) in 1:1 molar ratio at a gap of 48 h. Urinary and fecal elimination of cadmium and its distribution in liver, kidneys and spleen were examined. Treatment with TTHA encapsulated in liposomes mobilized higher amount of cadmium from liver and spleen. The overall efficiency for cadmium mobilization was better in TTHA encapsulated in SM:Chol liposome treated group which also led to enhanced excretion of cadmium through urine and feces. The results indicate that TTHA encapsulated in SM:Chol liposomes exhibited highest efficacy in mobilizing cadmium from the body of pre-exposed mice followed by PC:Chol liposomes and the free drug.