A novel diselenide attenuates the carrageenan-induced inflammation by reducing neutrophil infiltration and the resulting tissue damage in mice
Creators: name: dos Santos Lessa, Tássia Liz Araújo
name: Correia, Thiago Macêdo Lopes
name: dos Santos, Talita Costa
name: da Silva, Railmara Pereira
name: da Silva, Beatriz Pereira
name: Cavallini, Maria Cláudia Magalhães
name: Rocha, Leonardo Silva
name: Peixoto, Albert Souza
name: Cugnasca, Beatriz S.
name: Cervi, Gustavo
name: Correra, Thiago C.
name: Gonçalves, Augusto Cesar
name: Festuccia, William Tadeu Lara
name: Cunha, Thiago Mattar
name: Yatsuda, Regiane
name: de Magalhães, Amélia Cristina Mendes
name: Dos Santos, Alcindo A.
name: Meotti, Flávia Carla
name: Queiroz, Raphael Ferreira
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biochemistry
subject: Space Science
subject: Microbiology
subject: FOS: Biological sciences
subject: Cell Biology
subject: Molecular Biology
subject: Physiology
subject: Pharmacology
subject: Environmental Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences

description: Selenium-containing compounds have emerged as promising treatment for redox-based and inflammatory diseases. This study aimed to investigate the <i>in vitro</i> and <i>in vivo</i> anti-inflammatory activity of a novel diselenide named as dibenzyl[diselanediyIbis(propane-3-1diyl)] dicarbamate (DD). DD reacted with HOCl (<i>k</i> = 9.2 x 10<sup>7</sup> M<sup>−1</sup>s<sup>−1</sup>), like glutathione (<i>k</i> = 1.2 x 10<sup>8</sup> M<sup>−1</sup>s<sup>−1</sup>), yielding seleninic and selenonic acid derivatives, and it also decreased HOCl formation by activated human neutrophils (IC<sub>50</sub>=4.6 μM) and purified myeloperoxidase (MPO) (IC<sub>50</sub>=3.8 μM). However, tyrosine, MPO-I and MPO-II substrates, did not restore HOCl formation in presence of DD. DD inhibited the oxidative burst in <i>d</i>HL-60 cells with no toxicity up to 25 µM for 48h. Next, an intraperitoneal administration of 25, 50, and 75 mg/kg DD decreased total leukocyte, neutrophil chemotaxis, and inflammation markers (MPO activity, lipid peroxidation, albumin exudation, nitrite, TNF-α, IL-1β, CXCL1/KC, and CXCL2/MIP-2) on a murine model of carrageenan-induced peritonitis. Likewise, 50 mg/kg DD (i.p.) decreased carrageenan-induced paw edema over 5h. Histological and immunohistochemistry analyses of the paw tissue showed decreased neutrophil count, edema area, and MPO, carbonylated, and nitrated protein staining. Furthermore, DD treatment decreased the fMLP-induced chemotaxis of human neutrophils (IC<sub>50</sub>=3.7 μM) <i>in vitro</i> with no toxicity. Lastly, DD presented no toxicity in a single-dose model using mice (50 mg/kg, i.p.) over 15 days and in <i>Artemia salina</i> bioassay (50 to 2000 µM), corroborating findings from <i>in silico</i> toxicological study. Altogether, these results demonstrate that DD attenuates carrageenan-induced inflammation mainly by reducing neutrophil migration and the resulting damage from MPO-mediated oxidative burst.