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Morita-Baylis-Hillman Adduct 2-(3-Hydroxy-2-oxoindolin-3-yl)acrylonitrile (ISACN) Modulates Inflammatory Process In vitro and In vivo

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Abstract

Morita-Baylis-Hillman adducts (MBHA) are synthetic molecules with several biological actions already described in the literature. It has been previously described that adduct 2-(3-hydroxy-2-oxoindolin-3-yl)acrylonitrile (ISACN) has anticancer potential in leukemic cells. Inflammation is often associated with the development and progression of cancer. Therefore, to better understand the effect of ISACN, this study aimed to evaluate the anti-inflammatory potential of ISACN both in vitro and in vivo. Results demonstrated that ISACN negatively modulated the production of inflammatory cytokines IL-1β, TNF-α, and IL-6 by cultured macrophages. In vivo, ISACN 6 and 24 mg/kg treatment promoted reduced leukocyte migration, especially neutrophils, to the peritoneal cavity of zymosan-challenged animals. ISACN displays no anti-edematogenic activity, but it was able to promote a significant reduction in the production of inflammatory cytokines in the peritoneal cavity. These data show, for the first time, that MBHA ISACN negatively modulates several aspects of the inflammatory response, such as cell migration and cytokine production in vivo and in vitro, thus having an anti-inflammatory potential.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Funding

This research was supported partly by a grant from the “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior” (CAPES), PROCAD Grant Number 2951/2014, and by a fellowship from “Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).”

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Authors and Affiliations

  1. Centro de Ciências da Saúde, Universidade Federal da Paraíba, Joao Pessoa, PB 58051-900, Brazil

    Juliane Santos de França, José Marreiro de Sales-Neto & Sandra Rodrigues-Mascarenhas

  2. Laboratório de Imunobiotecnologia, Centro de Biotecnologia, Universidade Federal da Paraíba, Joao Pessoa, PB, CEP: 58051-900, Brazil

    Deyse Cristina Madruga Carvalho, Éssia de Almeida Lima & Sandra Rodrigues-Mascarenhas

  3. Centro de Ciências Exatas e Naturais, Universidade Federal da Paraíba, Joao Pessoa, PB, Brazil

    Tayná Rodrigues Olegário, Rhuan Karlos Santos Mendes, Claudio Gabriel Lima-Junior & Mário Luiz Araújo de Almeida Vasconcellos

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  1. Juliane Santos de França
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Contributions

Conceptualization, methodology, investigation, and writing—original draft: Silva J. S. F.. Investigation: Sales-Neto, J. M., and Lima, E. A.. Investigation and formal analysis: Carvalho, D. C. M. Resources: Olegário, T. R., Mendes, R. K. S., Lima-Junior, C. G., and Vasconcellos, M. L. A. A.. Conceptualization, resources, supervision, project administration, funding acquisition. Writing—review & editing: Rodrigues-Mascarenhas, S.

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de França, J.S., de Sales-Neto, J.M., Carvalho, D.C.M. et al. Morita-Baylis-Hillman Adduct 2-(3-Hydroxy-2-oxoindolin-3-yl)acrylonitrile (ISACN) Modulates Inflammatory Process In vitro and In vivo. Inflammation 44, 899–907 (2021). https://doi.org/10.1007/s10753-020-01385-9

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