Estudo comparativo entre estibogluconato de sódio BP 88R e antimoniato de meglumina no tratamento da leishmaniose cutânea: I. Eficácia e segurança

Saldanha, Ana Cristina R.; Romero, Gustavo; Merchán-Hamann, Edgar; Magalhães, Albino Verçosa de; Macêdo, Vanize

doi:10.1590/s0037-86821999000400008

Cited by 26 publications

(15 citation statements)

References 6 publications

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“…The proteinase activities (in solution) of the serine proteinase-enriched fraction (0.5 g of total proteins) and trypsin, which was used as a positive activity control, were characterized in activation buffer (10 mM Tris-HCl [pH 7.5]), at a final volume of 60 l, using specific fluorescent peptide substrates for serine proteinase (Z-FR-AMC, AFK-AMC, and Z-GGR-M␤NA at 0.1 mM). Samples were incubated for 60 min at 37°C, and the variance in the relative fluorescence units (RFU), corresponding to enzymatic cleavage of the substrates, was monitored with a Molecular Devices SpectraMax spectrophotometer (Gemini XPS) (7). Concomitantly, the efficacy of various serine proteinase inhibitors was assessed under the same conditions.…”

Section: Methodsmentioning

confidence: 99%

“…The currently available treatments for these infections are restricted to two option groups, namely, (i) the antimonials, which are the first-choice drugs (5,6), and (ii) pentamidine and amphotericin B, the second-choice drugs (7). Both groups of drugs have many limitations regarding their use, such as (i) high cost, (ii) difficulty of administration, (iii) toxicity, and (iv) the development of resistance by parasite strains.…”

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confidence: 99%

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Epoxy-α-Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

Souza-Silva

Bourguignon

Pereira

et al. 2015

Antimicrob Agents Chemother

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Leishmania (Leishmania) amazonensis is a protozoan that causes infections with a broad spectrum of clinical manifestations. The currently available chemotherapeutic treatments present many problems, such as several adverse side effects and the development of resistant strains. Natural compounds have been investigated as potential antileishmanial agents, and the effects of epoxy-␣-lapachone on L. (L.) amazonensis were analyzed in the present study. This compound was able to cause measurable effects on promastigote and amastigote forms of the parasite, affecting plasma membrane organization and leading to death after 3 h of exposure. This compound also had an effect in experimentally infected BALB/c mice, causing reductions in paw lesions 6 weeks after treatment with 0.44 mM epoxy-␣-lapachone (mean lesion area, 24.9 ؎ 2.0 mm 2 ), compared to untreated animals (mean lesion area, 30.8 ؎ 2.6 mm 2 ) or animals treated with Glucantime (mean lesion area, 28.3 ؎ 1.5 mm 2 ). In addition, the effects of this compound on the serine proteinase activities of the parasite were evaluated. Serine proteinase-enriched fractions were extracted from both promastigotes and amastigotes and were shown to act on specific serine proteinase substrates and to be sensitive to classic serine proteinase inhibitors (phenylmethylsulfonyl fluoride, aprotinin, and antipain). These fractions were also affected by epoxy-␣-lapachone. Furthermore, in silico simulations indicated that epoxy-␣-lapachone can bind to oligopeptidase B (OPB) of L. (L.) amazonensis, a serine proteinase, in a manner similar to that of antipain, interacting with an S1 binding site. This evidence suggests that OPB may be a potential target for epoxy-␣-lapachone and, as such, may be related to the compound's effects on the parasite.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Epoxy-α-Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

Souza-Silva

Bourguignon

Pereira

et al. 2015

Antimicrob Agents Chemother

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“…Mialgias, artralgias e febre são os efeitos colaterais comuns e todos freqüentemente são dependentes da dose e do tempo de tratamento 1 2 6 7 8 9 . O presente estudo teve como objetivo comparar a toxicidade hepática, pancreática, renal e cardíaca produzida pelo antimoniato de meglumina (Rhodia, São Paulo, Brasil) e o estibogluconato de sódio BP 88® (Shandong Xinhua, China) em pacientes com leishmaniose cutânea (LC) na área endêmica do Distrito de Corte de Pedra, Presidente Tancredo Neves, Bahia, Brasil, durante um estudo experimental aberto realizado para comparar a eficácia dos dois compostos 14 . Nesta região ocorre transmissão predominante de Leishmania (Viannia) braziliensis 12 .…”

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Estudo comparativo entre estibogluconato de sódio BP 88® e antimoniato de meglumina no tratamento da leishmaniose cutânea II. Toxicidade bioquímica e cardíaca

Saldanha

Romero

Guerra³

et al. 2000

Rev. Soc. Bras. Med. Trop.

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Foi avaliada a toxicidade de dois antimoniais pentavalentes em 111 pacientes com leishmaniose cutânea. Quarenta e sete pacientes receberam antimoniato de meglumina (Grupo I) e 64 pacientes, estibogluconato de sódio BP 88® (Grupo II), 20mg SbV/kg/dia por 20 dias. Realizou-se a avaliação de aminotransferases, fosfatase alcalina, amilase, creatinina, uréia, exame de urina e eletrocardiograma, antes do tratamento e no décimo e vigésimo dias. Observou-se maior freqüência de valores anormais de aminotransferases no décimo e vigésimo dias de tratamento no grupo II (p < 0,001) e maior proporção de valores anormais de amilase no décimo dia no mesmo grupo (p < 0,001). Houve maior variação dos níveis de aminotransferases, fosfatase alcalina e amilase nos primeiros dez dias no grupo II (p < 0,01). No vigésimo dia observou-se maior variação nos níveis de aminotransferases no grupo II (p = 0,02 e p = 0,03, respectivamente). Quarenta e três porcento dos pacientes do grupo I e 54% dos pacientes do grupo II apresentaram alterações eletrocardiográficas (p = 0,30).

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“…Esto está de acuerdo con los estudios de Sampaio et al (24) y Saldanha et al (25) que encontraron al estibogluconato de sodio más tóxico que el antimoniato de meglumina; se destaca la mayor frecuencia de cefaleas (p=0,026) mialgias/artralgias (p=0,004) y dolor abdominal/anorexia (p= 0,004).…”

Section: Discussionunclassified

Eficacia y toxicidad de los antimoniales pentavalentes (Glucantime y Pentostam) en un modelo animal de leishmaniasis cutánea americana: aplicación de la luminometría.

et al. 2004

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Los antimoniales pentavalentes Glucantime® y Pentostam® son los medicamentos de primera línea usados en el tratamiento anti-Leishmania; sin embargo, no hay estudios in vivo que comparen su eficacia y toxicidad controlando variables del hospedero. Los estudios bioquímicos en Leishmania detectaron diferencias entre los dos medicamentos en la inhibición de la topoisomerasa I, que podrían reflejarse en diferencias en su efectividad. Para evaluar la eficacia clínica se infectaron hámsteres en la pata trasera derecha con 10 6 promastigotes de Leishmania panamensis silvestre y transfectada con el gen de la luciferasa. Para evaluar la eficacia parasitológica se estandarizó la cuantificación de parásitos en los tejidos por luminometría. Tres semanas después de la inoculación, los animales se trataron intramuscularmente con Glucantime® o Pentostam® (30, 60 o 120 mg de Sb V /kg por día por 20 días). La toxicidad se evaluó en hámsteres tratados intramuscularmente con 120, 160 o 240 mg de Sb V /kg por día por 20 días de Glucantime® o Pentostam®. La resolución de las lesiones en los animales inoculados con ambas cepas fue similar con ambos medicamentos. La carga parasitaria disminuyó de forma equivalente con ambos medicamentos en todas las dosis, y resultó en diferencias significativas con respecto a los controles (p<0,01). Los niveles séricos de creatinina, aspartato aminotransferasa, alanino aminotransferasa y amilasa no evidenciaron alteraciones hepáticas o renales. Los animales tratados con dosis iguales o mayores de 120 mg de Sb V /kg por día por 20 días de Pentostam® presentaron alteraciones inflamatorias micro y macroscópicas en el sitio de la inyección que no se observaron en los tratados con Glucantime®. Estos resultados confirman observaciones clínicas sobre la eficacia similar de ambos productos e indican una toxicidad local mayor del Pentostam®.Palabras clave: hámster, Leishmania panamensis, leishmaniasis/tratamiento, antimonio pentavalente, Glucantime®, Pentostam®, transfección, luminometría. Efficacy and toxicity of pentavalent antimonials (Glucantime® and Pentostam®) in an American cutaneous leishmaniasis animal model: luminometry applicationThe pentavalent antimonial compounds Glucantime® and Pentostam® are the first line drugs used in anti-Leishmania treatment. However, no in vivo studies have compared the efficacy and toxicity of these drugs where host variability has been controlled. Biochemical studies of Leishmania have detected differences between the two drugs with regard to DNA topoisomerase I inhibition, a phenomenon that possibly impacts treatment efficacy. To evaluate the clinical efficacy, hamsters were infected intradermally in the right hind foot with 10 6 promastigotes of a wild type or luciferase-transfected Leishmania panamensis. At three weeks post-inoculation, the animals were treated intramuscularly with either Glucantime® or Pentostam® (30, 60 or 120 mg Sb V /kg per day for 20 days). To evaluate parasitological efficacy a luminometry assay was standardized for quantitation of amastigotes i...

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Estudo comparativo entre estibogluconato de sódio BP 88R e antimoniato de meglumina no tratamento da leishmaniose cutânea: I. Eficácia e segurança

Abstract: ResumoComparative study between sodium stibogluconate BP 88 R and meglumine antimoniate for cutaneous leishmaniasis treatment: I. Efficacy and safety

Cited by 26 publications

References 6 publications

Epoxy-α-Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

Epoxy-α-Lapachone Has In Vitro and In Vivo Anti-Leishmania (Leishmania) amazonensis Effects and Inhibits Serine Proteinase Activity in This Parasite

Estudo comparativo entre estibogluconato de sódio BP 88® e antimoniato de meglumina no tratamento da leishmaniose cutânea II. Toxicidade bioquímica e cardíaca

Eficacia y toxicidad de los antimoniales pentavalentes (Glucantime y Pentostam) en un modelo animal de leishmaniasis cutánea americana: aplicación de la luminometría.

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