Clinical treatment of cutaneous leishmaniasis in dogs with furazolidone and domperidone

Passos, Sônia Regina Lambert; Rodrigues, Tadeu de Azevedo; Madureira, Ana Paula; Giunchetti, Rodolfo Cordeiro; Zanini, Marcos Santos

doi:10.1016/j.ijantimicag.2014.07.011

Cited by 19 publications

(9 citation statements)

References 14 publications

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“…Furazolidone (FZD), a synthetic nitrofuran drug, has been used to treat the infections caused by bacteria and protozoa in human and animals [1,2]. Recent literatures report that FZD has novel applications in treating leukemia [3] or leishmaniasis [4]. In particular, FZD is usually used as a low-cost and effective drug to treat infections caused by Helicobacter pylori in human in developing countries, including China [5].…”

Section: Introductionmentioning

confidence: 99%

Curcumin Ameliorates Furazolidone-Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells by Inhibiting ROS Production and Mitochondrial Pathway

Dai

Gong

et al. 2016

Molecules

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Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD-induced cytotoxicity and the underlying mechanism in human hepatocyte L02 cells. The results showed that curcumin pre-treatment significantly ameliorated FZD-induced oxidative stress, characterized by decreased reactive oxygen species (ROS) and malondialdehyde formation, and increased superoxide dismutase, catalase activities and glutathione contents. In addition, curcumin pre-treatment significantly ameliorated the loss of mitochondrial membrane potential, the activations of caspase-9 and -3, and apoptosis caused by FZD. Alkaline comet assay showed that curcumin markedly reduced FZD-induced DNA damage in a dose-dependent manner. Curcumin pre-treatment consistently and markedly down-regulated the mRNA expression levels of p53, Bax, caspase-9 and -3 and up-regulated the mRNA expression level of Bcl-2. Taken together, these results reveal that curcumin protects against FZD-induced DNA damage and apoptosis by inhibiting oxidative stress and mitochondrial pathway. Our study indicated that curcumin may be a promising combiner with FZD to reduce FZD-related toxicity in clinical applications.

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Section: Introductionmentioning

confidence: 99%

Curcumin Ameliorates Furazolidone-Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells by Inhibiting ROS Production and Mitochondrial Pathway

Dai

Gong

et al. 2016

Molecules

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“…A leishmaniose está envolvida em diversos mecanismos imunológicos associados ao aumento da produção de globulinas (Freitas et al, 2012), o que explica o aumento das proteínas totais observadas nesse caso. A hipoalbuminemia pode ser justificada pelo aumento no catabolismo proteico devido a ocorrência de caquexia, alterações na função hepática devido a progressão da doença (Passos et al, 2014), e ainda neste caso devido a inflamação persistente pois a albumina é considerada uma proteína de fase aguda negativa e também pela presença de proteinúria. Esta última observada no paciente é considerada um achado importante na LVC, podendo ocorrer devido à glomerulonefrite ocasionada pela deposição de imunocomplexos no glomérulo (Freitas et al, 2012).…”

Section: Discussionunclassified

Leishmaniose visceral canina na região norte do estado do Rio Grande do Sul

Garcia

Silva

Ampese

et al. 2022

RSD

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A leishmaniose é uma doença zoonótica causada pelo protozoário da espécie Leishmania spp., diagnosticada com pouca frequência em cães da região norte do Rio Grande do Sul (RS). Devido a isso, casos alóctones se tornam importantes para investigação. O objetivo deste trabalho é relatar um caso de leishmaniose visceral em um canino e enfatizar seus aspectos clínicos, diagnósticos e terapêuticos. Foi atendido um cão da raça Pug com 3 anos, proveniente de Araranguá, no estado de Santa Catarina (SC), com queixa principal de hiporexia, prostração, onicogrifose e algia em membros pélvicos. O paciente fazia uso de imunossupressores há dois meses devido a presença de poliartrite. Ao exame clínico, observou-se nódulo cutâneo e aumento de linfonodos poplíteos. Realizada citologia por agulha fina de ambos locais, onde foram observadas formas amastigotas de Leishmania spp. O caso foi notificado aos órgãos competentes e realizado sorologia pelo método de Elisa para confirmação do diagnóstico. Instituiu-se tratamento com miltefosina, domperidona, alopurinol e vacina Leish Tec®. Evidencia-se a importância de minuciosa anamnese associada a realização de exames laboratoriais para triagem de pacientes portadores da doença, com foco na possibilidade de casos alóctones serem diagnosticados em regiões não endêmicas do Brasil.

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“…Instead of focusing on antimicrobial agents, we selected compounds belonging to a wide spectrum of pharmacological classes (Table 1). There are no data in the literature about the antileishmanial activities of glimepiride and ezetimibe, but interestingly, domperidone has been used in clinical trials, aiming at veterinary use, with naturally infected dogs (16,17). However, in those studies, no intrinsic antileishmanial activity was assigned to domperidone.…”

Section: Discussionmentioning

confidence: 99%

“…However, in those studies, no intrinsic antileishmanial activity was assigned to domperidone. The therapeutic effect of this drug in dogs has been attributed to its immunomodulatory activity (17).…”

Section: Discussionmentioning

confidence: 99%

Antileishmanial Activity of Ezetimibe: Inhibition of Sterol Biosynthesis, In Vitro Synergy with Azoles, and Efficacy in Experimental Cutaneous Leishmaniasis

Andrade-Neto

Cunha-Júnior

Canto‐Cavalheiro

et al. 2016

Antimicrob Agents Chemother

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Leishmaniasis affects mainly low-income populations in tropical regions. Radical innovation in drug discovery is time-consuming and expensive, imposing severe restrictions on the ability to launch new chemical entities for the treatment of neglected diseases. Drug repositioning is an attractive strategy for addressing a specific demand more easily. In this project, we have evaluated the antileishmanial activities of 30 drugs currently in clinical use for various morbidities. Ezetimibe, clinically used to reduce intestinal cholesterol absorption in dyslipidemic patients, killed Leishmania amazonensis promastigotes with a 50% inhibitory concentration (IC 50 ) of 30 M. Morphological analysis revealed that ezetimibe caused the parasites to become rounded, with multiple nuclei and flagella. Analysis by gas chromatography (GC)-mass spectrometry (MS) showed that promastigotes treated with ezetimibe had smaller amounts of C-14-demethylated sterols, and accumulated more cholesterol and lanosterol, than untreated promastigotes. We then evaluated the combination of ezetimibe with well-known antileishmanial azoles. The fractional inhibitory concentration index (FICI) indicated synergy when ezetimibe was combined with ketoconazole or miconazole. The activity of ezetimibe against intracellular amastigotes was confirmed, with an IC 50 of 20 M, and ezetimibe reduced the IC 90 s of ketoconazole and miconazole from 11.3 and 11.5 M to 4.14 and 8.25 M, respectively. Subsequently, we confirmed the activity of ezetimibe in vivo, showing that it decreased lesion development and parasite loads in murine cutaneous leishmaniasis. We concluded that ezetimibe has promising antileishmanial activity and should be considered in combination with azoles in further preclinical and clinical studies.

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Clinical treatment of cutaneous leishmaniasis in dogs with furazolidone and domperidone

Cited by 19 publications

References 14 publications

Curcumin Ameliorates Furazolidone-Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells by Inhibiting ROS Production and Mitochondrial Pathway

Curcumin Ameliorates Furazolidone-Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells by Inhibiting ROS Production and Mitochondrial Pathway

Leishmaniose visceral canina na região norte do estado do Rio Grande do Sul

Antileishmanial Activity of Ezetimibe: Inhibition of Sterol Biosynthesis, In Vitro Synergy with Azoles, and Efficacy in Experimental Cutaneous Leishmaniasis

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