1. Decorporation and therapeutic efficacy of liposomal-DTPA against thorium-induced toxicity in the Wistar rat.
- Author
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Kumar, Amit, Sharma, Pragya, Ali, Manjoor, Pandey, Badri Narain, and Mishra, Kaushala Prasad
- Subjects
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DIETHYLENETRIAMINEPENTAACETIC acid , *LIPOSOMES , *DRUG efficacy , *THORIUM , *OXIDATIVE stress , *LABORATORY rats , *CELL-mediated cytotoxicity - Abstract
Purpose: This study examined the effect of liposomal encapsulation of 99mTc-labeled diethylenetriaminepentaacetic acid (metastable technetium labeled DTPA) on its organ distribution and therapeutic effect of optimized neutral liposomal-DTPA against thorium (232Th)-induced liver toxicity and its accumulation in rat animal model. Materials and methods: 99mTc-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 232Th accumulation and subsequent toxicity in the liver and blood of rat administered with 232Th-nitrate (600 μg/kg). Organ distribution of free or liposomal 99mTc-DTPA was determined by solid scintillation counting and 232Th accumulation by Inductively Coupled Plasma-Atomic Emission Spectroscopy. Results: Neutral liposomes encapsulated with 99mTc-DTPA showed more uptake in liver, spleen and blood than with positively charged liposomal- and free- 99mTc-DTPA. Administration of 232Th-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 232Th 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 232Th induced toxicity may be significantly improved by liposomal encapsulation of DTPA, a chelating agent. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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