Sanjay Gupta

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.

Effect of intratracheal injection of zinc oxide dust in guinea pigs.

Intratracheal injection of zinc oxide dust, a component of many cosmetic preparations caused elevation of alkaline phosphatase and lactate dehydrogenase in serum and lung of guinea pigs. Clearance of zinc oxide dust from lungs through zinc-carrying proteins was evident.

Effect of liposome encapsulated meso-2,3-dimercaptosuccinic acid (DMSA) on biochemical and trace metal alterations in cadmium exposed rats

Cadmium a well known occupational and environmental contaminant, causes damage to body organs, particularly to kidneys. Considerable attention has been paid towards the development of safe and effective chelation therapy in the management of cadmium poisoning. The present communication deals with the use of liposome encapsulated DMSA, a known thiol chelator for the treatment of cadmium intoxicated rats which was found to be effective in restoring cadmium mediated biochemical and trace metal alterations.

Modulation of liposomal lipid peroxidation in presence of nickel by incorporation of a-tocopherol in the bilayer

alpha-Tocopherol is a well-known membrane associated chain-breaking phenolic antioxidant which functions as a trap for peroxyl and other free radicals and thus inhibits lipid peroxidation of membranes. Antioxidative effect of alpha-tocopherol when incorporated in liposomes was examined by the generation of Thiobarbituric acid (TBA) reacting species in the presence of nickel. The incorporation of alpha-tocopherol in the lipid bilayer resulted in the enhancement of lipid peroxidation at low concentration (1.0 mg) but at higher concentration (2.5 and 5.0 mg) considerably reduced the enhancement in lipid peroxidation of liposomes in the presence of nickel. When alpha-tocopherol was added (unincorporated) to liposomes in the presence of nickel, enhancement in lipid peroxidation was observed compared to nickel alone. Thus the antioxidative effect of alpha-tocopherol in the liposomes may depend on its mode of incorporation in the lipid bilayer.

Alkaline phosphatase as a model for studying metal-protein interactions in pulmonary toxicity

An attempt has been made to study the biochemical properties of lung alkaline phosphatase so that it may serve as a model for measuring the toxicity of air pollutants, especially metals. Lung was shown to be a better source of this enzyme in comparison to other organs in rats. The optimum pH, metal requirements, substrate specificity, and affinity constants were characterized with different substrates, and the effect of different metals was studied. The involvement of zinc in the lung enzyme was not indicated as shown by Sephadex G-200 elution profile of postmitochondrial supernatant of 65Zn-treated animals.

Use of liposome encapsulated sodium‐ 2,3‐dimercapto‐propane sulfonate (DMPS) in the treatment of mice loaded with cadmium

Abstract Sodium‐2, 3‐dimercaptopropane sulfonate (DMPS) is a potent thiol chelating drug used against heavy metal intoxication. With a view to enhance its efficacy at low dose DMPS was encapsulated in liposomes made up of equimolar egg phosphotidylcholine and cholesterol and then administered to mice loaded with cadmium. Both the free as well as liposomal drug enhanced urinary excretion of cadmium. While fecal excretion of cadmium was enhanced only by liposomal drug, liposomal DMPS was effective in mobilizing more cadmium from blood, liver, kidney and spleen by day 3 of treatment, Liposomal DMPS was also able to decorporate some cadmium from cadmium binding proteins with low molecular weight corresponding to metallothionein.