Enhanced thorium decorporation and mitigation of toxicity through combined use of Liv52® and diethylenetriamine pentaacetate

Thorium-232 (Th-232) is a promising fuel for advanced nuclear reactors. However, in case of internal human exposure to Th, there is currently no effective modality for its removal from liver and skeleton or for mitigating its effect. The FDA-approved agent, diethylenetriaminepentaacetate (DTPA), can...

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Bibliographic Details
Published in:Journal of hazardous materials 2024-09, Vol.477, p.135234, Article 135234
Main Authors: Ali, Manjoor, Kumar Das, Sourav, Shetake, Neena G., Pandey, B.N., Kumar, Amit
Format: Article
Language:English
Subjects:
DTPA
L52S
Mitigation of toxicity
Thorium decorporation
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Summary:Thorium-232 (Th-232) is a promising fuel for advanced nuclear reactors. However, in case of internal human exposure to Th, there is currently no effective modality for its removal from liver and skeleton or for mitigating its effect. The FDA-approved agent, diethylenetriaminepentaacetate (DTPA), can remove Th and other actinides from blood circulation only. For the first time, a rationally-selected polyherbal hepatoprotective i.e. Liv52® (L52S), was evaluated in-combination with DTPA for its Th decorporation ability in Swiss mice. Inductively-coupled plasma mass spectroscopic analysis showed that oral administration of L52S in conjunction with DTPA significantly decreased Th burden from liver (20 %) and skeleton (33 %) as well as enhanced Th excretion (∼2.5 folds) through urine in comparison to DTPA or L52S alone. The combinatorial therapy was found to be complementary in-action, ameliorating Th-induced tissue damage in liver, spleen, and bone more effectively than monotherapy. Furthermore, markers of liver function (alanine transaminase) and liver inflammation and fibrosis (NF-κB & keratin) further validated the beneficial effect of L52S. The human consumption of L52S for various liver disorders further supports its clinical application for Th decorporation and mitigation of its health effects. [Display omitted] ●L52S in-combination with DTPA enhanced urinary excretion of Th by 2.4 fold.●L52S + DTPA significantly decreased Th in liver and skeleton (20-33 %).●L52S + DTPA profoundly mitigated Th-induced damage in target organs.●L52S remarkably reduced (20 %) markers of liver inflammation and fibrosis.
ISSN:0304-3894
1873-3336
1873-3336
DOI:10.1016/j.jhazmat.2024.135234