Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/17770 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ. Brasil. |
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Cunha Junior, Edézio FerreiraMartins, Thiago MartinoCavalheiro, Marilene Marcuzzo CantoMarques, Paulo RobertoPortari, Elyzabeth AvvadCoelho, Marsen Garcia PintoNetto, Chaquip DaherCosta, Paulo Roberto RibeiroSabino, Katia Costa de CarvalhoSantos, Eduardo Caio Torres2017-02-09T14:45:46Z2017-02-09T14:45:46Z2016CUNHA JUNIOR, Edézio Ferreira; et al. Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis. Antimicrobial Agents and Chemotherapy, v.60, n.6, p.3794-3801, June 2016.0066-4804https://www.arca.fiocruz.br/handle/icict/1777010.1128/AAC.01787-151098-6596engAmerican Society for MicrobiologyLeishmaniose visceralToxicidade subagudaEficácia TerapêuticaPterocarpanquinonaVisceral leishmaniasisSubacute ToxicityTherapeutic efficacyLQB-118Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ. Brasil.Universidade do Estado do Rio de Janeiro. Laboratório Imunol. Aplicada e Bioq. de Proteínas e Prod. Naturais. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ. Brasil.Universidade do Estado do Rio de Janeiro. Laboratório Imunol. Aplicada e Bioq. de Proteínas e Prod. Naturais. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Departamento de Patologia e Laboratórios. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Laboratório Imunol. Aplicada e Bioq. de Proteínas e Prod. Naturais. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Laboratório de Química. Macaé, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Pesquisas de Produtos Naturais. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Laboratório Imunol. Aplicada e Bioq. de Proteínas e Prod. Naturais. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ. Brasil.Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/17770/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALedesio_cunhajr_etal_IOC_2016.pdfedesio_cunhajr_etal_IOC_2016.pdfapplication/pdf2057722https://www.arca.fiocruz.br/bitstream/icict/17770/2/edesio_cunhajr_etal_IOC_2016.pdfb905a7232a9bd50caaeeaa9c5415f825MD52zac007165262so1.pdfzac007165262so1.pdfMaterial 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| dc.title.pt_BR.fl_str_mv |
Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis |
| title |
Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis |
| spellingShingle |
Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis Cunha Junior, Edézio Ferreira Leishmaniose visceral Toxicidade subaguda Eficácia Terapêutica Pterocarpanquinona Visceral leishmaniasis Subacute Toxicity Therapeutic efficacy LQB-118 |
| title_short |
Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis |
| title_full |
Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis |
| title_fullStr |
Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis |
| title_full_unstemmed |
Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis |
| title_sort |
Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis |
| author |
Cunha Junior, Edézio Ferreira |
| author_facet |
Cunha Junior, Edézio Ferreira Martins, Thiago Martino Cavalheiro, Marilene Marcuzzo Canto Marques, Paulo Roberto Portari, Elyzabeth Avvad Coelho, Marsen Garcia Pinto Netto, Chaquip Daher Costa, Paulo Roberto Ribeiro Sabino, Katia Costa de Carvalho Santos, Eduardo Caio Torres |
| author_role |
author |
| author2 |
Martins, Thiago Martino Cavalheiro, Marilene Marcuzzo Canto Marques, Paulo Roberto Portari, Elyzabeth Avvad Coelho, Marsen Garcia Pinto Netto, Chaquip Daher Costa, Paulo Roberto Ribeiro Sabino, Katia Costa de Carvalho Santos, Eduardo Caio Torres |
| author2_role |
author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Cunha Junior, Edézio Ferreira Martins, Thiago Martino Cavalheiro, Marilene Marcuzzo Canto Marques, Paulo Roberto Portari, Elyzabeth Avvad Coelho, Marsen Garcia Pinto Netto, Chaquip Daher Costa, Paulo Roberto Ribeiro Sabino, Katia Costa de Carvalho Santos, Eduardo Caio Torres |
| dc.subject.other.pt_BR.fl_str_mv |
Leishmaniose visceral Toxicidade subaguda Eficácia Terapêutica Pterocarpanquinona |
| topic |
Leishmaniose visceral Toxicidade subaguda Eficácia Terapêutica Pterocarpanquinona Visceral leishmaniasis Subacute Toxicity Therapeutic efficacy LQB-118 |
| dc.subject.en.pt_BR.fl_str_mv |
Visceral leishmaniasis Subacute Toxicity Therapeutic efficacy LQB-118 |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ. Brasil. |
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2016 |
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2016 |
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2017-02-09T14:45:46Z |
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2017-02-09T14:45:46Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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CUNHA JUNIOR, Edézio Ferreira; et al. Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis. Antimicrobial Agents and Chemotherapy, v.60, n.6, p.3794-3801, June 2016. |
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https://www.arca.fiocruz.br/handle/icict/17770 |
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0066-4804 |
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10.1128/AAC.01787-15 |
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1098-6596 |
| identifier_str_mv |
CUNHA JUNIOR, Edézio Ferreira; et al. Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis. Antimicrobial Agents and Chemotherapy, v.60, n.6, p.3794-3801, June 2016. 0066-4804 10.1128/AAC.01787-15 1098-6596 |
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American Society for Microbiology |
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American Society for Microbiology |
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