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Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral leishmaniasis.

Castro RA, Silva-Barcellos NM, Licio CS, Souza JB, Souza-Testasicca MC, Ferreira FM, Batista MA, Silveira-Lemos D, Moura SL, Frézard F, Rezende SA - PLoS ONE (2014)

Bottom Line: Considering the lack of an effective vaccine the afflicted population must rely on both, an accurate diagnosis and successful treatment to combat the disease.Treatment with liposome-encapsulated SbIII significantly reduced the parasite burden in the liver, spleen and bone marrow.Of particular importance, reduction of parasite burden in the bone marrow attested to the ability of SbIII-carrying liposomes to efficiently reach this body compartment.

View Article: PubMed Central - PubMed

Affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas - Cipharma, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brasil.

ABSTRACT

Background: Visceral leishmaniasis (VL) is a chronic debilitating disease endemic in tropical and subtropical areas, caused by protozoan parasites of the genus Leishmania. Annually, it is estimated the occurrence of 0.2 to 0.4 million new cases of the disease worldwide. Considering the lack of an effective vaccine the afflicted population must rely on both, an accurate diagnosis and successful treatment to combat the disease. Here we propose to evaluate the efficacy of trivalent antimonial encapsulated in conventional liposomes, in association with ascorbic acid, by monitoring its toxicity and efficacy in BALB/c mice infected with Leishmania infantum.

Methodology/principal findings: Infected mice were subjected to single-dose treatments consisting in the administration of either free or liposome-encapsulated trivalent antimony (SbIII), in association or not with ascorbic acid. Parasite burden was assessed in the liver, spleen and bone marrow using the serial limiting dilution technique. After treatment, tissue alterations were examined by histopathology of liver, heart and kidney and confirmed by serum levels of classic biomarkers. The phenotypic profile of splenocytes was also investigated by flow cytometry. Treatment with liposome-encapsulated SbIII significantly reduced the parasite burden in the liver, spleen and bone marrow. Co-administration of ascorbic acid, with either free SbIII or its liposomal form, did not interfere with its leishmanicidal activity and promoted reduced toxicity particularly to the kidney and liver tissues.

Conclusions/significance: Among the evaluated posological regimens treatment of L. infantum-infected mice with liposomal SbIII, in association with ascorbic acid, represented the best alternative as judged by its high leishmanicidal activity and absence of detectable toxic effects. Of particular importance, reduction of parasite burden in the bone marrow attested to the ability of SbIII-carrying liposomes to efficiently reach this body compartment.

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Histopathological analyses of the kidney from L. infantum infected mice submitted to different treatment regimens.(A) Phosphate-buffered saline (PBS). (B) Empty liposomes (Empty Lipo). (C) Trivalent antimony (Sb). (D) Antimony entrapped liposomes (Sb Lipo). (E) Ascorbic acid (AA). (F) Ascorbic acid in association with antimony (AA+Sb). (G) Ascorbic acid in association with antimony entrapped liposomes (AA+Sb Lipo). Bar  = 50 µm. Insert  = 25 µm, representing glomerular hyperemia. (A), (B) and (E) renal parenchyma exhibiting normal aspect. (C), (D), (F) and (G) renal parenchyma exhibiting active hyperemia. * Hyperemic vessels.
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pone-0104055-g006: Histopathological analyses of the kidney from L. infantum infected mice submitted to different treatment regimens.(A) Phosphate-buffered saline (PBS). (B) Empty liposomes (Empty Lipo). (C) Trivalent antimony (Sb). (D) Antimony entrapped liposomes (Sb Lipo). (E) Ascorbic acid (AA). (F) Ascorbic acid in association with antimony (AA+Sb). (G) Ascorbic acid in association with antimony entrapped liposomes (AA+Sb Lipo). Bar  = 50 µm. Insert  = 25 µm, representing glomerular hyperemia. (A), (B) and (E) renal parenchyma exhibiting normal aspect. (C), (D), (F) and (G) renal parenchyma exhibiting active hyperemia. * Hyperemic vessels.

Mentions: In the kidney tissue, no alterations in the morphology of glomerular mesangial cells, glomerulonephritis or the presence of hyaline intratubular cylinders were observed in any of the treated groups. The hyperemia found in the cardiac tissue was also notable in the kidney for animals undergoing SbIII treatment (Figure 6C, 6D, 6F and 6G, asterisked areas). Nevertheless, in the kidney hyperemia varied from discrete to moderate. Remarkably, treatment with liposome-entrapped SbIII promoted a reduction in the glomerular congestion (Figure 6D), which was also much alleviated when such regimen was applied in association with ascorbic acid (Figure 6G).


Association of liposome-encapsulated trivalent antimonial with ascorbic acid: an effective and safe strategy in the treatment of experimental visceral leishmaniasis.

Castro RA, Silva-Barcellos NM, Licio CS, Souza JB, Souza-Testasicca MC, Ferreira FM, Batista MA, Silveira-Lemos D, Moura SL, Frézard F, Rezende SA - PLoS ONE (2014)

Histopathological analyses of the kidney from L. infantum infected mice submitted to different treatment regimens.(A) Phosphate-buffered saline (PBS). (B) Empty liposomes (Empty Lipo). (C) Trivalent antimony (Sb). (D) Antimony entrapped liposomes (Sb Lipo). (E) Ascorbic acid (AA). (F) Ascorbic acid in association with antimony (AA+Sb). (G) Ascorbic acid in association with antimony entrapped liposomes (AA+Sb Lipo). Bar  = 50 µm. Insert  = 25 µm, representing glomerular hyperemia. (A), (B) and (E) renal parenchyma exhibiting normal aspect. (C), (D), (F) and (G) renal parenchyma exhibiting active hyperemia. * Hyperemic vessels.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126701&req=5

pone-0104055-g006: Histopathological analyses of the kidney from L. infantum infected mice submitted to different treatment regimens.(A) Phosphate-buffered saline (PBS). (B) Empty liposomes (Empty Lipo). (C) Trivalent antimony (Sb). (D) Antimony entrapped liposomes (Sb Lipo). (E) Ascorbic acid (AA). (F) Ascorbic acid in association with antimony (AA+Sb). (G) Ascorbic acid in association with antimony entrapped liposomes (AA+Sb Lipo). Bar  = 50 µm. Insert  = 25 µm, representing glomerular hyperemia. (A), (B) and (E) renal parenchyma exhibiting normal aspect. (C), (D), (F) and (G) renal parenchyma exhibiting active hyperemia. * Hyperemic vessels.
Mentions: In the kidney tissue, no alterations in the morphology of glomerular mesangial cells, glomerulonephritis or the presence of hyaline intratubular cylinders were observed in any of the treated groups. The hyperemia found in the cardiac tissue was also notable in the kidney for animals undergoing SbIII treatment (Figure 6C, 6D, 6F and 6G, asterisked areas). Nevertheless, in the kidney hyperemia varied from discrete to moderate. Remarkably, treatment with liposome-entrapped SbIII promoted a reduction in the glomerular congestion (Figure 6D), which was also much alleviated when such regimen was applied in association with ascorbic acid (Figure 6G).

Bottom Line: Considering the lack of an effective vaccine the afflicted population must rely on both, an accurate diagnosis and successful treatment to combat the disease.Treatment with liposome-encapsulated SbIII significantly reduced the parasite burden in the liver, spleen and bone marrow.Of particular importance, reduction of parasite burden in the bone marrow attested to the ability of SbIII-carrying liposomes to efficiently reach this body compartment.

View Article: PubMed Central - PubMed

Affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas - Cipharma, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brasil.

ABSTRACT

Background: Visceral leishmaniasis (VL) is a chronic debilitating disease endemic in tropical and subtropical areas, caused by protozoan parasites of the genus Leishmania. Annually, it is estimated the occurrence of 0.2 to 0.4 million new cases of the disease worldwide. Considering the lack of an effective vaccine the afflicted population must rely on both, an accurate diagnosis and successful treatment to combat the disease. Here we propose to evaluate the efficacy of trivalent antimonial encapsulated in conventional liposomes, in association with ascorbic acid, by monitoring its toxicity and efficacy in BALB/c mice infected with Leishmania infantum.

Methodology/principal findings: Infected mice were subjected to single-dose treatments consisting in the administration of either free or liposome-encapsulated trivalent antimony (SbIII), in association or not with ascorbic acid. Parasite burden was assessed in the liver, spleen and bone marrow using the serial limiting dilution technique. After treatment, tissue alterations were examined by histopathology of liver, heart and kidney and confirmed by serum levels of classic biomarkers. The phenotypic profile of splenocytes was also investigated by flow cytometry. Treatment with liposome-encapsulated SbIII significantly reduced the parasite burden in the liver, spleen and bone marrow. Co-administration of ascorbic acid, with either free SbIII or its liposomal form, did not interfere with its leishmanicidal activity and promoted reduced toxicity particularly to the kidney and liver tissues.

Conclusions/significance: Among the evaluated posological regimens treatment of L. infantum-infected mice with liposomal SbIII, in association with ascorbic acid, represented the best alternative as judged by its high leishmanicidal activity and absence of detectable toxic effects. Of particular importance, reduction of parasite burden in the bone marrow attested to the ability of SbIII-carrying liposomes to efficiently reach this body compartment.

Show MeSH
Related in: MedlinePlus