Limits...
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.

Show MeSH

Related in: MedlinePlus

Parasite burden associated to the liver, spleen and bone marrow from L. infantum infected mice.Parasite burden is expressed as log10 (number of parasites) +1 for each individual organ (n = 4, per experimental group) and represented as median ± interquartile range of two independent experiments. Statistically significant differences were assumed when p<0,05 in relation to (a) two weeks post-infection and (b) four weeks post-infection.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4126701&req=5

pone-0104055-g001: Parasite burden associated to the liver, spleen and bone marrow from L. infantum infected mice.Parasite burden is expressed as log10 (number of parasites) +1 for each individual organ (n = 4, per experimental group) and represented as median ± interquartile range of two independent experiments. Statistically significant differences were assumed when p<0,05 in relation to (a) two weeks post-infection and (b) four weeks post-infection.

Mentions: Before quantification of the leishmanicidal activity of liposome-encapsulated SbIII, we first sought to determine the parasite burden associated to the liver, spleen and bone marrow during the 2nd to 8th week's post-infection interval. The limiting dilution technique revealed the presence of the parasite at significant levels in the liver and spleen at the 2nd week post-infection (Figure 1). Parasite levels associated with these organs did not vary significantly for mice euthanized at the 4th, 6th and 8th weeks post-infection. On average, parasite burden in the liver was approximately 50% higher than that observed for the spleen. Comparatively, very low levels of parasites were detected in the bone marrow at the 2nd and 4th weeks post-infection. In contrast, at the 6th week post-infection parasite levels in the bone marrow reached 16% of that found in the liver increasing to approximately 20% in animals euthanized at the 8th week post infection. At this point, parasite levels in the bone marrow reached 42% of those found in the spleen.


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)

Parasite burden associated to the liver, spleen and bone marrow from L. infantum infected mice.Parasite burden is expressed as log10 (number of parasites) +1 for each individual organ (n = 4, per experimental group) and represented as median ± interquartile range of two independent experiments. Statistically significant differences were assumed when p<0,05 in relation to (a) two weeks post-infection and (b) four weeks post-infection.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0104055-g001: Parasite burden associated to the liver, spleen and bone marrow from L. infantum infected mice.Parasite burden is expressed as log10 (number of parasites) +1 for each individual organ (n = 4, per experimental group) and represented as median ± interquartile range of two independent experiments. Statistically significant differences were assumed when p<0,05 in relation to (a) two weeks post-infection and (b) four weeks post-infection.
Mentions: Before quantification of the leishmanicidal activity of liposome-encapsulated SbIII, we first sought to determine the parasite burden associated to the liver, spleen and bone marrow during the 2nd to 8th week's post-infection interval. The limiting dilution technique revealed the presence of the parasite at significant levels in the liver and spleen at the 2nd week post-infection (Figure 1). Parasite levels associated with these organs did not vary significantly for mice euthanized at the 4th, 6th and 8th weeks post-infection. On average, parasite burden in the liver was approximately 50% higher than that observed for the spleen. Comparatively, very low levels of parasites were detected in the bone marrow at the 2nd and 4th weeks post-infection. In contrast, at the 6th week post-infection parasite levels in the bone marrow reached 16% of that found in the liver increasing to approximately 20% in animals euthanized at the 8th week post infection. At this point, parasite levels in the bone marrow reached 42% of those found in the spleen.

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