1.A Novel Organotellurium Compound (RT-01) as a New Antileishmanial Agent.
Camila Barbara Cantalupo LIMA ; Wagner Welber ARRAIS-SILVA ; Rodrigo Luiz Oliveira Rodrigues CUNHA ; Selma GIORGIO
The Korean Journal of Parasitology 2009;47(3):213-218
Leishmaniasis is a neglected disease and endemic in developing countries. A lack of adequate and definitive chemotherapeutic agents to fight against this infection has led to the investigation of numerous compounds. The aim of this study was to investigate the effect of RT-01, an organotellurane compound presenting biological activities, in 2 experimental systems against Leishmania amazonensis. The in vitro system consisted of promastigotes and amastigotes forms of the parasite, and the in vivo system consisted of L. amazonensis infected BALB/c mice, an extremely susceptible mouse strain. The compound proved to be toxic against promastigotes and amastigotes. The study also showed that treatment with RT-01 produces an effect similar to that treatment with the reference antimonial drug, Glucantime, in L. amazonensis infected mice. The best results were obtained following RT-01 intralesional administration (720 microgram/kg/day); mice showed significant delay in the development of cutaneous lesions and decreased numbers of parasites obtained from the lesions. Significant differences in tissue pathology consisted mainly of no expressive accumulation of inflammatory cells and well-preserved structures in the skin tissue of RT-01-treated mice compared with expressive infiltration of infected cells replacing the skin tissue in lesions of untreated mice. These findings highlight the fact that the apparent potency of organotellurane compounds, together with their relatively simple structure, may represent a new avenue for the development of novel drugs to combat parasitic diseases.
Animals
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Antiprotozoal Agents/*pharmacology
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Disease Models, Animal
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Female
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Humans
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Leishmania mexicana/*drug effects
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Leishmaniasis/drug therapy/*parasitology
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Mice
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Mice, Inbred BALB C
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Organometallic Compounds/*pharmacology
2.A Novel Organotellurium Compound (RT-01) as a New Antileishmanial Agent.
Camila Barbara Cantalupo LIMA ; Wagner Welber ARRAIS-SILVA ; Rodrigo Luiz Oliveira Rodrigues CUNHA ; Selma GIORGIO
The Korean Journal of Parasitology 2009;47(3):213-218
Leishmaniasis is a neglected disease and endemic in developing countries. A lack of adequate and definitive chemotherapeutic agents to fight against this infection has led to the investigation of numerous compounds. The aim of this study was to investigate the effect of RT-01, an organotellurane compound presenting biological activities, in 2 experimental systems against Leishmania amazonensis. The in vitro system consisted of promastigotes and amastigotes forms of the parasite, and the in vivo system consisted of L. amazonensis infected BALB/c mice, an extremely susceptible mouse strain. The compound proved to be toxic against promastigotes and amastigotes. The study also showed that treatment with RT-01 produces an effect similar to that treatment with the reference antimonial drug, Glucantime, in L. amazonensis infected mice. The best results were obtained following RT-01 intralesional administration (720 microgram/kg/day); mice showed significant delay in the development of cutaneous lesions and decreased numbers of parasites obtained from the lesions. Significant differences in tissue pathology consisted mainly of no expressive accumulation of inflammatory cells and well-preserved structures in the skin tissue of RT-01-treated mice compared with expressive infiltration of infected cells replacing the skin tissue in lesions of untreated mice. These findings highlight the fact that the apparent potency of organotellurane compounds, together with their relatively simple structure, may represent a new avenue for the development of novel drugs to combat parasitic diseases.
Animals
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Antiprotozoal Agents/*pharmacology
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Disease Models, Animal
;
Female
;
Humans
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Leishmania mexicana/*drug effects
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Leishmaniasis/drug therapy/*parasitology
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Mice
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Mice, Inbred BALB C
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Organometallic Compounds/*pharmacology
3.Use of In Vivo and In Vitro Systems to Select Leishmania amazonensis Expressing Green Fluorescent Protein.
Solange dos Santos COSTA ; Marjorie DE ASSIS GOLIM ; Bartira ROSSI-BERGMANN ; Fabio Trindade Maranhao COSTA ; Selma GIORGIO
The Korean Journal of Parasitology 2011;49(4):357-364
Various Leishmania species were engineered with green fluorescent protein (GFP) using episomal vectors that encoded an antibiotic resistance gene, such as aminoglycoside geneticin sulphate (G418). Most reports of GFP-Leishmania have used the flagellated extracellular promastigote, the stage of parasite detected in the midgut of the sandfly vector; fewer studies have been performed with amastigotes, the stage of parasite detected in mammals. In this study, comparisons were made regarding the efficiency for in vitro G418 selection of GFP-Leishmania amazonensis promastigotes and amastigotes and the use of in vivo G418 selection. The GFP-promastigotes retained episomal plasmid for a prolonged period and G418 treatment was necessary and efficient for in vitro selection. In contrast, GFP-amastigotes showed low retention of the episomal plasmid in the absence of G418 selection and low sensitivity to antibiotics in vitro. The use of protocols for G418 selection using infected BALB/c mice also indicated low sensitivity to antibiotics against amastigotes in cutaneous lesions.
Amebicides/*pharmacology
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Animals
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Flow Cytometry
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Gentamicins/*pharmacology
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Green Fluorescent Proteins/*chemistry
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Host-Parasite Interactions
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Leishmania mexicana/drug effects/genetics/*growth & development
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Leishmaniasis, Cutaneous/*parasitology
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Luminescent Agents/*chemistry
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Macrophages, Peritoneal/parasitology
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Mice
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Mice, Inbred BALB C
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Organisms, Genetically Modified
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Spectrometry, Fluorescence
4.Aureobasidium-Derived Soluble Branched (1,3-1,6) beta-Glucan (Sophy beta-glucan) Enhances Natural Killer Activity in Leishmania amazonensis-Infected Mice.
Lalani YATAWARA ; Susiji WICKRAMASINGHE ; Mitsuru NAGATAKI ; Misa TAKAMOTO ; Haruka NOMURA ; Yasunori IKEUE ; Yoshiya WATANABE ; Takeshi AGATSUMA
The Korean Journal of Parasitology 2009;47(4):345-351
The beta-glucans derived from yeast cell walls have been reported for having many immunomodulatory activities in vivo and in vitro. In this study, Aureobasidium-derived soluble branched (1,3-1,6) beta-glucan (Sophy beta-glucan) was checked for natural killer (NK) activity and for the production of IFN-gamma and IL-4 in Leishmania amazonensis infection. The main experiment was performed with a group of female C57BL/6 and BALB/c mice, orally supplemented with 5% of Sophy beta-glucan and infected with promastogotes of L. amazonensis (1 x 10(7)) into the footpad. Increase in the footpad thickness with time was observed in BALB/c mice in spite of the oral Sophy beta-glucan supplement, but it was less in C57BL/6 mice. The difference in overall mean footpad thickness between 'infection only' versus 'infection + glucan' groups was statistically significant (P < 0.001). High NK activity in C57BL/6 than BALB/c mice was observed in 'glucan only' group compared to the control group and also in 'infection + glucan' group compared to 'infection only' group. The difference in the NK activity among these groups was significant (P < 0.05). The IFN-gamma level increased at weeks 7 and 8 post-infection in C57BL/6 mice and was significantly high in 'infection + glucan' group compared to the 'infection only' group (P < 0.05). IL-4 levels did not increase up to detectable levels throughout the study. The results led a conclusion that Sophy beta-glucan enhances NK activity and cellular immunity in L. amazonensis-infected mice.
Administration, Oral
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Animals
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Ascomycota/*chemistry
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Cytotoxicity Tests, Immunologic
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Female
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Foot/pathology
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Glucans/administration & dosage/*isolation & purification/pharmacology/*therapeutic use
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Immunologic Factors/administration & dosage/*isolation & purification/pharmacology/*therapeutic use
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Interferon-gamma/biosynthesis
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Interleukin-4/biosynthesis
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Killer Cells, Natural/drug effects/*immunology
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Leishmania mexicana/*immunology
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Leishmaniasis, Cutaneous/*drug therapy/immunology/pathology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Severity of Illness Index
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Time Factors