Avaliação da atividade inibitória da epóxido hidrolase solúvel induzida por droga na inflamação pulmonar

Abstract

Background: Several enzymes act on regulatory pathways of factors that modulate pulmonary responses, including inflammatory enzymes. The inflammatory processes that occur in the lung are linked to tissue damage processes and organ functional loss. Thus, evaluating the inflammatory enzymatic interactions related to pulmonary functions collaborate to generate intervention indicators or even prophylactic measures that improve the patient's prognosis. The inhibition of the epoxide hydrolase enzyme using GSK2256294 has been considered as promising in clinical and preclinical models for pulmonary inflammatory processes associated with tobacco, COPD or obesity, however the discrepancies between effect sizes in the types of models have not yet been raised. Considering that some synthetic epoxide hydrolase inhibitors do not have inhibitory effectiveness, it is important to evaluate the reproducibility of the models. Objective: Thus, the present study evaluated possible discrepancies between the effects of the inhibition of epoxide hydrolase by GSK2256294 in different models of pulmonary inflammation. Methods: A secondary study was carried out in the scientific databases Medline (PubMed), Web of Science, Scielo, cochrane library, embase, academic google and gray literature. The searches were carried out by 2 independent reviewers, delimiting the records between the period from 2012 to 2021. Duplicate articles that did not fit the scope of the research were excluded. The methodological quality and consistency of evidence were analyzed. Meta-analysis was applied to compare the different variables. Result: A total of 86 studies were found in the different study bases, with 4 of these studies selected in the gray literature. After applying the eligibility criteria, 3 studies were classified and evaluated. However, GSK2256294 was able to reduce the soluble epoxide hydrolase enzyme in both clinical and preclinical study models, but with greater effectiveness in clinical studies. In addition, it collaborates in the anti-inflammatory activity mediated by the eicosatrienoic pathway, both by reducing DHETS and Leukotoxin-diol. It also helps in controlling blood flow. Conclusion: The present study demonstrated that GSK2256294 is a promising drug in the control of the deleterious manifestations observed in lung inflammation, however, due to the small number of articles retrieved from the databases, further studies are needed to ensure consistency of evidence and allow for unraveling. other routes of biological activities mediated by GSK2256294 for clinical and preclinical studies. Protocol registration: The study was registered in the Open Science Framework database (OSF Registers) under registration Doi: 10.17605/OSF.IO/PMHA8 and structured according to the Protocol Preferred Reporting Items for Systematic reviews and Meta-Analyses.