scholarly journals Differences in cNOS/iNOS Activity during Resistance to Trypanosoma cruzi Infection in 5-Lipoxygenase Knockout Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Carolina Panis ◽  
Vanessa Jacob Victorino ◽  
Vera Lúcia Hideko Tatakihara ◽  
Rubens Cecchini ◽  
Luiz Vicente Rizzo ◽  
...  

Infection with the protozoan Trypanosoma cruzi causes Chagas disease and consequently leads to severe inflammatory heart condition; however, the mechanisms driving this inflammatory response have not been completely elucidated. Nitric oxide (NO) is a key mediator of parasite killing in T. cruzi-infected mice, and previous studies have suggested that leukotrienes (LTs) essentially regulate the NO activity in the heart. We used infected 5-lipoxygenase-deficient mice (5-LO−/−) to explore the participation of nitric oxide synthase isoforms, inducible (iNOS) and constitutive (cNOS), in heart injury, cytokine profile, and oxidative stress during the early stage of T. cruzi infection. Our evidence suggests that the cNOS of the host is involved in the resistance of 5-LO−/− mice during T. cruzi infection. iNOS inhibition generated a remarkable increase in T. cruzi infection in the blood and heart of mice, whereas cNOS inhibition reduced cardiac parasitism (amastigote nests). Furthermore, this inhibition associates with a higher IFN-γ production and lower lipid peroxidation status. These data provide a better understanding about the influence of NO-interfering therapies for the inflammatory response toward T. cruzi infection.

1997 ◽  
Vol 6 (3) ◽  
pp. 161-166 ◽  
Author(s):  
Huan Huang, MD ◽  
John Chan, MD ◽  
Murray Wittner, MD, PhD ◽  
Louis M Weiss, MD, MPH ◽  
J Bacchi, PhD ◽  
...  

2018 ◽  
Vol 129 ◽  
pp. 227-236 ◽  
Author(s):  
Amanda A. Felizardo ◽  
Ivo S. Caldas ◽  
Andréa A.S. Mendonça ◽  
Reggiani V. Gonçalves ◽  
Fernanda L. Tana ◽  
...  

2012 ◽  
Vol 6 (5) ◽  
pp. e1644 ◽  
Author(s):  
Cristiano Marcelo Espinola Carvalho ◽  
Jaline Coutinho Silverio ◽  
Andrea Alice da Silva ◽  
Isabela Resende Pereira ◽  
Janice Mery Chicarino Coelho ◽  
...  

Placenta ◽  
2017 ◽  
Vol 51 ◽  
pp. 116-117
Author(s):  
M.F. Triquell ◽  
E. Benizio ◽  
M.J. Moreira-Espinoza ◽  
J.C. Ramírez ◽  
L. Mezzano ◽  
...  

2015 ◽  
Vol 227 ◽  
pp. 104-111 ◽  
Author(s):  
Vera Lucia Hideko Tatakihara ◽  
Aparecida Donizette Malvezi ◽  
Carolina Panis ◽  
Rubens Cecchini ◽  
Nagela Ghabdan Zanluqui ◽  
...  

2020 ◽  
Vol 19 (30) ◽  
pp. 2795-2804 ◽  
Author(s):  
Ricardo Pereira Rodrigues ◽  
Juliana Santa Ardisson ◽  
Rita de Cássia Ribeiro Gonçalves ◽  
Tiago Branquinho Oliveira ◽  
Vinicius Barreto da Silva ◽  
...  

Background: Helicobacter pylori is a gram-negative bacterium related to chronic gastritis, peptic ulcer and gastric carcinoma. During its infection process, promotes excessive inflammatory response, increasing the release of reactive species and inducing the production of pro-inflammatory mediators. Inducible Nitric Oxide Synthase (iNOS) plays a crucial role in the gastric carcinogenesis process and a key mediator of inflammation and host defense systems, which is expressed in macrophages induced by inflammatory stimuli. In chronic diseases such as Helicobacter pylori infections, the overproduction of NO due to the prolonged induction of iNOS is of major concern. Objective: In this sense, the search for potential iNOS inhibitors is a valuable strategy in the overall process of Helicobacter pylori pathogeny. Method: In silico techniques were applied in the search of interesting compounds against Inducible Nitric Oxide Synthase enzyme in a chemical space of natural products and derivatives from the Analyticon Discovery databases. Results: The five compounds with the best iNOS inhibition profile were selected for activity and toxicity predictions. Compound 9 (CAS 88198-99-6) displayed significant potential for iNOS inhibition, forming hydrogen bonds with residues from the active site and an ionic interaction with heme. This compound also displayed good bioavailability and absence of toxicity/or from its probable metabolites. Conclusion: The top-ranked compounds from the virtual screening workflow show promising results regarding the iNOS inhibition profile. The results evidenced the importance of the ionic bonding during docking selection, playing a crucial role in binding and positioning during ligand-target selection for iNOS.


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