Decorporation and therapeutic efficacy of liposomal-DTPA against thorium-induced toxicity in the Wistar rat. 2012

Amit Kumar, and Pragya Sharma, and Manjoor Ali, and Badri Narain Pandey, and Kaushala Prasad Mishra
Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, India.

OBJECTIVE This study examined the effect of liposomal encapsulation of (99m)Tc-labeled diethylenetriaminepentaacetic acid (metastable technetium labeled DTPA) on its organ distribution and therapeutic effect of optimized neutral liposomal-DTPA against thorium ((232)Th)-induced liver toxicity and its accumulation in rat animal model. METHODS (99m)Tc-DTPA was encapsulated in neutral (dipalmitoylphosphatidylcholine:cholesterol) and positively (dipalmitoylphosphatidylcholine:cholesterol:stearylamine) charged liposomes using thin film hydration method. Comparative efficacy of liposomal and free DTPA (11.2 mg/kg) was examined in terms of its effect on (232)Th accumulation and subsequent toxicity in the liver and blood of rat administered with (232)Th-nitrate (600 μg/kg). Organ distribution of free or liposomal (99m)Tc-DTPA was determined by solid scintillation counting and (232)Th accumulation by Inductively Coupled Plasma-Atomic Emission Spectroscopy. RESULTS Neutral liposomes encapsulated with (99m)Tc-DTPA showed more uptake in liver, spleen and blood than with positively charged liposomal- and free- (99m)Tc-DTPA. Administration of (232)Th-nitrate to rat significantly increased the levels of liver toxicity markers and of oxidative injury, which were found to be restored more significantly by neutral liposomal-DTPA than free-DTPA. The accumulation of (232)Th in liver and blood of contaminated mice was found to be decreased more significantly by neutral liposomal-DTPA than by free-DTPA. CONCLUSIONS Decorporation and consequent mitigation of (232)Th induced toxicity may be significantly improved by liposomal encapsulation of DTPA, a chelating agent.

UI MeSH Term Description Entries
D008081 Liposomes Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. Niosomes,Transferosomes,Ultradeformable Liposomes,Liposomes, Ultra-deformable,Liposome,Liposome, Ultra-deformable,Liposome, Ultradeformable,Liposomes, Ultra deformable,Liposomes, Ultradeformable,Niosome,Transferosome,Ultra-deformable Liposome,Ultra-deformable Liposomes,Ultradeformable Liposome
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D002614 Chelating Agents Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS. Chelating Agent,Chelator,Complexons,Metal Antagonists,Chelators,Metal Chelating Agents,Agent, Chelating,Agents, Chelating,Agents, Metal Chelating,Antagonists, Metal,Chelating Agents, Metal
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013910 Thorium A radioactive element of the actinide series of metals. It has an atomic symbol Th, atomic number 90, and atomic weight 232.04. It is used as fuel in nuclear reactors to produce fissionable uranium isotopes. Because of its radioopacity, various thorium compounds are used to facilitate visualization in roentgenography.
D016284 Technetium Tc 99m Pentetate A technetium imaging agent used in renal scintigraphy, computed tomography, lung ventilation imaging, gastrointestinal scintigraphy, and many other procedures which employ radionuclide imaging agents. Tc 99m-DTPA,Tc-DTPA,Technetium-DTPA,Technetium (99m) Pentetate,Technetium Pentetic Acid,Technetium diethylenetriamine pentaacetic acid,99m-DTPA, Tc,Pentetic Acid, Technetium,Tc 99m DTPA,Technetium DTPA
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative

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