Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate

Meglumine antimoniate (MA) and sodium stibogluconate are pentavalent antimony (SbV) drugs used since the mid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there are gaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distribution of antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from male rats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous). Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2 = 0.6 h) and a slow (t1/2 >> 24 h) elimination phase. The spleen was the organ that accumulated the highest amount of Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen >> bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain). The pathophysiological consequences of Sb accumulation in the thyroid and Sb speciation in the liver, thyroid, spleen and bone warrant further studies.

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Main Authors: Coelho,Deise Riba, Miranda,Elaine Silva, Saint?Pierre,Tatiana Dillenburg, Paumgartten,Francisco José Roma
Format: Digital revista
Language:English
Published: Instituto Oswaldo Cruz, Ministério da Saúde 2014
Online Access:http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762014000400420
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spelling oai:scielo:S0074-027620140004004202014-07-24Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniateCoelho,Deise RibaMiranda,Elaine SilvaSaint?Pierre,Tatiana DillenburgPaumgartten,Francisco José Roma pentavalent antimonials thyroid liver leishmaniases Glucantime pharmacokinetics Meglumine antimoniate (MA) and sodium stibogluconate are pentavalent antimony (SbV) drugs used since the mid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there are gaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distribution of antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from male rats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous). Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2 = 0.6 h) and a slow (t1/2 >> 24 h) elimination phase. The spleen was the organ that accumulated the highest amount of Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen >> bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain). The pathophysiological consequences of Sb accumulation in the thyroid and Sb speciation in the liver, thyroid, spleen and bone warrant further studies.info:eu-repo/semantics/openAccessInstituto Oswaldo Cruz, Ministério da SaúdeMemórias do Instituto Oswaldo Cruz v.109 n.4 20142014-07-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762014000400420en10.1590/0074-0276140030
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country Brasil
countrycode BR
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libraryname SciELO
language English
format Digital
author Coelho,Deise Riba
Miranda,Elaine Silva
Saint?Pierre,Tatiana Dillenburg
Paumgartten,Francisco José Roma
spellingShingle Coelho,Deise Riba
Miranda,Elaine Silva
Saint?Pierre,Tatiana Dillenburg
Paumgartten,Francisco José Roma
Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate
author_facet Coelho,Deise Riba
Miranda,Elaine Silva
Saint?Pierre,Tatiana Dillenburg
Paumgartten,Francisco José Roma
author_sort Coelho,Deise Riba
title Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate
title_short Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate
title_full Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate
title_fullStr Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate
title_full_unstemmed Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate
title_sort tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate
description Meglumine antimoniate (MA) and sodium stibogluconate are pentavalent antimony (SbV) drugs used since the mid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there are gaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distribution of antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from male rats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous). Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2 = 0.6 h) and a slow (t1/2 >> 24 h) elimination phase. The spleen was the organ that accumulated the highest amount of Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen >> bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain). The pathophysiological consequences of Sb accumulation in the thyroid and Sb speciation in the liver, thyroid, spleen and bone warrant further studies.
publisher Instituto Oswaldo Cruz, Ministério da Saúde
publishDate 2014
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762014000400420
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