Drug repurposing strategy against Trypanosoma cruzi infection: In vitro and in vivo assessment of the activity of metronidazole in mono- and combined therapy

2017 ◽  
Vol 145 ◽  
pp. 46-53 ◽  
Author(s):  
M.R. Simões-Silva ◽  
J.S. De Araújo ◽  
G.M. Oliveira ◽  
K.C. Demarque ◽  
R.B. Peres ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Combined Therapy ◽  
Drug Repurposing ◽  
Cruzi Infection ◽  
In Vivo Assessment

New 1,2,3-triazole-based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

2018 ◽  
Vol 92 (3) ◽  
pp. 1670-1682 ◽  
Author(s):  
Débora Inácio Leite ◽  
Fábio de Vasconcellos Fontes ◽  
Monica Macedo Bastos ◽  
Lucas Villas Boas Hoelz ◽  
Maria da Conceição Avelino Dias Bianco ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Cruzi Infection

In vitro and in vivo activity of voriconazole and benznidazole combination on trypanosoma cruzi infection models

Acta Tropica ◽  
2020 ◽  
Vol 211 ◽  
pp. 105606
Author(s):  
Julián Ernesto Nicolás Gulin ◽  
Mackenzie Anne Eagleson ◽  
Rodrigo A. López-Muñoz ◽  
María Elisa Solana ◽  
Jaime Altcheh ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Infection Models ◽  
Cruzi Infection

scholarly journals Drug Repurposing of Asparaginase and Vitamin C Targeting Glutamine Synthetase Improves Anticancer Effect in Metastatic Castration-resistant Prostate Cancer

2022 ◽  
Author(s):  
Zhoulei Li ◽  
Wanqing Shen ◽  
Zhifeng Chen ◽  
Gang Yuan ◽  
Peng He ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Glutamine Synthetase ◽  
Vitamin C ◽  
Combined Therapy ◽  
Drug Repurposing ◽  
Castration Resistant Prostate Cancer ◽  
Anticancer Effect ◽  
18F Fdg

Abstract Background: Although in North America or Europe early dignosis of prostate cancer could sucessfully improves the therapeutic outcome. However, about 70-80% of patients still suffer from metastatic castration-resistant prostate cancer (mCRPC), because of the disproportionate medical care in China. Lutetium-177 (Lu-177) or Radium-223 (Ra-223) has been suggested as the most effective therapy for mCRPC. Unfortunately, they are either not been approved in a few countries or too expensive for patients with the financial issue. Drug repurposing has been recognized as a cost-effective and relatively low-risk alternative, gains a lot interesting recently. In this study, we explored the combined treatment with asparaginase (ASNase) and/or vitamin Cas an alternative therapeutic option for mCRPC management.Methods: Prostate cancer cell lines PC3 and DU145 were used to observe the therapeutic effect of ASNase and/or vitamin C on mCRPC in vitro and in vivo. Change of cell proliferation, cell death as well as expression of glutamine synthetase eunder different treatment conditions were detected to analyzed anticancer effect of combined therapy with ASNase and vitamin C on mCRPC. Intracellular oxidation was also observed with NADPH and NADP+ assay. Male BALB/c nude mice bearing prostate carcinoma xenografts (PC3 or DU145) were used to assess treatment response to vitamin C with or without ASNase through tumor growth, small animal PET/CT scans as well as Immunohistochemistry in vivo.Results: Our in vitro studies demonstrate that ASNase synergizes with vitamin C targeting expression of glutamine synthetase enhances redox imbalance and induces anticancer effect in mCRPC cells through regulation the glutamine synthetase (GS) expression. In vivo, combination of ASnase and vitamin C could provide a significant better therapeutic outcome in comparison with controls or single treated mice. 18F-FDG PET imaging illustrated that the treatment with combined therapy could significantly reduce the 18F-FDG uptake in tumor.Conclusions: In this current study, we suggest that ASNase combined with vitamin C could be as a cost-effective strategy to manage mCRPC.18F-FDG PET/CT imaging could indicate the therapeutic response of treatment for mCRPC.

scholarly journals P100W4-2 Analysis of host cell apoptosis in vitro and in vivo by Trypanosoma cruzi infection

2001 ◽  
Vol 52 (Supplement) ◽  
pp. 102
Author(s):  
Junko SHIMADA ◽  
Chunbin ZOU ◽  
Takeshi NARA ◽  
Miriam PONSTAN ◽  
Takashi AOKI ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Host Cell ◽  
Cell Apoptosis ◽  
Host Cell Apoptosis ◽  
Cruzi Infection

Host and parasite apoptosis following Trypanosoma cruzi infection in in vitro and in vivo models

2003 ◽  
Vol 314 (2) ◽  
pp. 223-235 ◽  
Author(s):  
E. M. de Souza ◽  
T. C. Araújo-Jorge ◽  
C. Bailly ◽  
A. Lansiaux ◽  
M. M. Batista ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
In Vivo Models ◽  
Cruzi Infection

scholarly journals Repurposing Strategy of Atorvastatin against Trypanosoma cruzi: In Vitro Monotherapy and Combined Therapy with Benznidazole Exhibit Synergistic Trypanocidal Activity

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
C. F. Araujo-Lima ◽  
R. B. Peres ◽  
P. B. Silva ◽  
M. M. Batista ◽  
C. A. F. Aiub ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Combined Therapy ◽  
Fixed Ratio ◽  
Drug Repurposing ◽  
Biological Properties ◽  
Cardiac Cells ◽  
Content Type ◽  
Density Reduction ◽  
Different Strains

ABSTRACT Statins are inhibitors of cholesterol synthesis, but other biological properties, such as antimicrobial effects, have also been assigned to them, leading to their designation as pleiotropic agents. Our goal was to investigate the activity and selectivity of atorvastatin (AVA) against Trypanosoma cruzi by using in vitro models, aiming for more effective and safer therapeutic options through drug repurposing proposals for monotherapy and therapy in combination with benznidazole (BZ). Phenotypic screening was performed with different strains (Tulahuen [discrete typing unit {DTU} VI] and Y [DTU II]) and forms (intracellular forms, bloodstream trypomastigotes, and tissue-derived trypomastigotes) of the parasite. On assay of the Tulahuen strain, AVA was more active against intracellular amastigotes (selectivity index [SI] = 3). Also, against a parasite of another DTU (Y strain), this statin was more active (2.1-fold) and selective (2.4-fold) against bloodstream trypomastigotes (SI = 51) than against the intracellular forms (SI = 20). A cytomorphological approach using phalloidin-rhodamine permitted us to verify that AVA did not induced cell density reduction and that cardiac cells (CC) maintained their typical cytoarchitecture. Combinatory approaches using fixed-ratio methods showed that AVA and BZ gave synergistic interactions against both trypomastigotes and intracellular forms (mean sums of fractional inhibitory concentration indexes [∑FICIs] of 0.46 ± 0.12 and 0.48 ± 0.03, respectively). Thus, the repurposing strategy for AVA, especially in combination with BZ, which leads to a synergistic effect, is encouraging for future studies to identify novel therapeutic protocols for Chagas disease treatment.

scholarly journals Arthrospira maxima Paradoxical Effect on Trypanosoma cruzi-Infection

2020 ◽  
Author(s):  
Oscar A REBOREDA-HERNANDEZ ◽  
Adriana L. JUAREZ-SERRANO ◽  
Ivan GARCIA-LUNA ◽  
Nora L RIVERO-RAMIREZ ◽  
Rocio ORTIZ-BUTRON ◽  
...  
Keyword(s):  
Biological Sciences ◽  
Trypanosoma Cruzi ◽  
Early Death ◽  
Parasitic Infections ◽  
Paradoxical Effect ◽  
Macrophage Phagocytosis ◽  
Arthrospira Maxima ◽  
Cruzi Infection

Background: There are only two anti-trypanocidal drugs available, both have a lot of side effects. This is the pioneer study designed to evaluate the Arthrospira maxima effect in Trypanosoma cruzi -infected mice and macrophages. effect in Trypanosoma cruzi -infected mice and macrophages. Methods: A. maxima was administered in vivo, and in vitro (120µL/mL; 200 µL/mL; 500 µL/mL; 852 µL/mL) as prophylaxis, and treatment. In vitro, phagocytosis and viability were measured in macrophages cultures supplemented with A. maxima, and T. cruzi-infected. In vivo A. maxima was supplemented to T. cruziinfected mice in order to obtain the parasitemia curves, parasite amount, and histopathologic changes. This assay was performed in Biological Sciences National School of National Polytechnic Institute, Mexico City, in 2019. Results: In vivo, A. maxima administration exacerbates the immune innate host´s response, followed by mice early death. In vitro, A. maxima supplementation promote T. cruzi- macrophage phagocytosis, but also a sooner T. cruzi- infected macrophage death. Conclusion: A. maxima administration overactive the immune system, decreasing the parasitemia, but causing a severe tissue damage. Then, this nutraceutical has a paradoxical effect on intracellular parasitic infections such as Chagas disease.

scholarly journals Trypanosoma cruzi infection induces up-regulation of cardiac muscarinic acetylcholine receptors in vivo and in vitro

2008 ◽  
Vol 41 (9) ◽  
pp. 796-803 ◽  
Author(s):  
K. Peraza-Cruces ◽  
L. Gutiérrez-Guédez ◽  
D. Castañeda Perozo ◽  
C.R. Lankford ◽  
C. Rodríguez-Bonfante ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Acetylcholine Receptors ◽  
Muscarinic Acetylcholine Receptors ◽  
Muscarinic Acetylcholine ◽  
Cruzi Infection

scholarly journals In Vitro, In Vivo, and In Silico Studies of Cumanin Diacetate as a Potential Drug against Trypanosoma cruzi Infection

ACS Omega ◽  
2021 ◽  
Author(s):  
Andrés Sánchez Alberti ◽  
María F. Beer ◽  
Natacha Cerny ◽  
Augusto E. Bivona ◽  
Lucas Fabian ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
In Silico ◽  
Potential Drug ◽  
In Silico Studies ◽  
Cruzi Infection
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