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

Coelho DR, Miranda ES, Saint'Pierre TD, Paumgartten FJ - Mem. Inst. Oswaldo Cruz (2014)

Bottom Line: Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Toxicologia Ambiental, Departamento de Ciências Biológicas, Escola Nacional de Saúde Pública-Fiocruz, Rio de Janeiro, RJ, Brasil.

ABSTRACT
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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: tissues the residual antimony levels of which were lower than 5 µg/g. Sbcontent (µg/g, dry wt) was determined by inductively coupled plasma-massspectrometry in rats killed 24 h (n = 6) and 21 days (n = 6) after a 21-dtreatment with meglumine antimoniate (MA) (300 mg SbV/kg body wt/d,subcutaneous). Asterisks mean a decrease (Student t test, p< 0.05) of Sb concentration within three weeks of the end of MAadministration
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f04: : tissues the residual antimony levels of which were lower than 5 µg/g. Sbcontent (µg/g, dry wt) was determined by inductively coupled plasma-massspectrometry in rats killed 24 h (n = 6) and 21 days (n = 6) after a 21-dtreatment with meglumine antimoniate (MA) (300 mg SbV/kg body wt/d,subcutaneous). Asterisks mean a decrease (Student t test, p< 0.05) of Sb concentration within three weeks of the end of MAadministration

Mentions: Residual levels of Sb in tissues after a 21-day course of treatment with MA -Tissue concentrations of Sb were determined in rats killed 24 h after the lastdose of MA and in a second group of animals killed 21 days after treatmentdiscontinuation (Table I). Fig. 3 shows the distribution of Sb in the spleen, kidneys, femur,thyroid, liver, epididymis, lungs and adrenals, all of which presented Sb levels higherthan 5 µg/g at the end of treatment. The spleen ranked first among the tissues with thehighest levels of Sb at the end of treatment. Although declining markedly over athree-week post-treatment period, levels of Sb in the spleen were still the highestamong all tissues on day 42 (Table I). Thekidneys, bones (femur) and thyroid gland ranked second in a descending order of Sbcontent in tissues at the end of MA administration period (Table I). In contrast to the bones and thyroid, the Sb levels whichexhibited a small reduction, kidney levels showed a drastic decline during the threepost-treatment weeks. The liver, epididymis, lungs and adrenals showed intermediatelevels of Sb at the end of treatment (Table I).On day 42, levels of Sb in the liver and epididymis were markedly lower than the levelson the day after the last dose of MA, while levels in lungs and adrenals were modestlyreduced. Fig. 4 presents tissues that showed thelowest concentrations of Sb (< 5 µg/g) after a course of treatment with MA. Thetissues with low (< 5 µg/g) Sb concentrations on day 22 that exhibited a furtherreduction of metalloid content within the next three weeks were as follows: prostate,thymus, small intestine, skeletal muscle, testes and stomach. The tissues which did notexhibit a discernible change in Sb levels between days 22-42 were pancreas, heart andbrain (Table I).


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

Coelho DR, Miranda ES, Saint'Pierre TD, Paumgartten FJ - Mem. Inst. Oswaldo Cruz (2014)

: tissues the residual antimony levels of which were lower than 5 µg/g. Sbcontent (µg/g, dry wt) was determined by inductively coupled plasma-massspectrometry in rats killed 24 h (n = 6) and 21 days (n = 6) after a 21-dtreatment with meglumine antimoniate (MA) (300 mg SbV/kg body wt/d,subcutaneous). Asterisks mean a decrease (Student t test, p< 0.05) of Sb concentration within three weeks of the end of MAadministration
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4155842&req=5

f04: : tissues the residual antimony levels of which were lower than 5 µg/g. Sbcontent (µg/g, dry wt) was determined by inductively coupled plasma-massspectrometry in rats killed 24 h (n = 6) and 21 days (n = 6) after a 21-dtreatment with meglumine antimoniate (MA) (300 mg SbV/kg body wt/d,subcutaneous). Asterisks mean a decrease (Student t test, p< 0.05) of Sb concentration within three weeks of the end of MAadministration
Mentions: Residual levels of Sb in tissues after a 21-day course of treatment with MA -Tissue concentrations of Sb were determined in rats killed 24 h after the lastdose of MA and in a second group of animals killed 21 days after treatmentdiscontinuation (Table I). Fig. 3 shows the distribution of Sb in the spleen, kidneys, femur,thyroid, liver, epididymis, lungs and adrenals, all of which presented Sb levels higherthan 5 µg/g at the end of treatment. The spleen ranked first among the tissues with thehighest levels of Sb at the end of treatment. Although declining markedly over athree-week post-treatment period, levels of Sb in the spleen were still the highestamong all tissues on day 42 (Table I). Thekidneys, bones (femur) and thyroid gland ranked second in a descending order of Sbcontent in tissues at the end of MA administration period (Table I). In contrast to the bones and thyroid, the Sb levels whichexhibited a small reduction, kidney levels showed a drastic decline during the threepost-treatment weeks. The liver, epididymis, lungs and adrenals showed intermediatelevels of Sb at the end of treatment (Table I).On day 42, levels of Sb in the liver and epididymis were markedly lower than the levelson the day after the last dose of MA, while levels in lungs and adrenals were modestlyreduced. Fig. 4 presents tissues that showed thelowest concentrations of Sb (< 5 µg/g) after a course of treatment with MA. Thetissues with low (< 5 µg/g) Sb concentrations on day 22 that exhibited a furtherreduction of metalloid content within the next three weeks were as follows: prostate,thymus, small intestine, skeletal muscle, testes and stomach. The tissues which did notexhibit a discernible change in Sb levels between days 22-42 were pancreas, heart andbrain (Table I).

Bottom Line: Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Toxicologia Ambiental, Departamento de Ciências Biológicas, Escola Nacional de Saúde Pública-Fiocruz, Rio de Janeiro, RJ, Brasil.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus