A novel diselenide attenuates the carrageenan-induced inflammation by reducing neutrophil infiltration and the resulting tissue damage in mice
Selenium-containing compounds have emerged as promising treatment for redox-based and inflammatory diseases. This study aimed to investigate the in vitro and in vivo anti-inflammatory activity of a novel diselenide named as dibenzyl[diselanediyIbis(propane-3-1diyl)] dicarbamate (DD). DD reacted with HOCl (k = 9.2 x 107 M-1s-1), like glutathione (k = 1.2 x 108 M-1s-1), yielding seleninic and selenonic acid derivatives, and it also decreased HOCl formation by activated human neutrophils (IC50=4.6 μM) and purified myeloperoxidase (MPO) (IC50=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 dHL-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 (IC50=3.7 μM) in vitro 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 Artemia salina bioassay (50 to 2000 µM), corroborating findings from in silico 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Free radical research - (2024) vom: 08. Apr., Seite 1-20 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lessa, Tássia Liz Araújo Dos Santos [VerfasserIn] |
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| Links: |
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| Themen: |
Hypochlorous acid |
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| Anmerkungen: |
Date Revised 25.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1080/10715762.2024.2336566 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370777573 |
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| 100 | 1 | |a Lessa, Tássia Liz Araújo Dos Santos |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A novel diselenide attenuates the carrageenan-induced inflammation by reducing neutrophil infiltration and the resulting tissue damage in mice |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 25.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Selenium-containing compounds have emerged as promising treatment for redox-based and inflammatory diseases. This study aimed to investigate the in vitro and in vivo anti-inflammatory activity of a novel diselenide named as dibenzyl[diselanediyIbis(propane-3-1diyl)] dicarbamate (DD). DD reacted with HOCl (k = 9.2 x 107 M-1s-1), like glutathione (k = 1.2 x 108 M-1s-1), yielding seleninic and selenonic acid derivatives, and it also decreased HOCl formation by activated human neutrophils (IC50=4.6 μM) and purified myeloperoxidase (MPO) (IC50=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 dHL-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 (IC50=3.7 μM) in vitro 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 Artemia salina bioassay (50 to 2000 µM), corroborating findings from in silico 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Selenium | |
| 650 | 4 | |a hypochlorous acid | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a myeloperoxidase | |
| 650 | 4 | |a neutrophil chemotaxis | |
| 650 | 4 | |a oxidative burst | |
| 700 | 1 | |a Correia, Thiago Macêdo Lopes |e verfasserin |4 aut | |
| 700 | 1 | |a Santos, Talita Costa Dos |e verfasserin |4 aut | |
| 700 | 1 | |a da Silva, Railmara Pereira |e verfasserin |4 aut | |
| 700 | 1 | |a Silva, Beatriz Pereira da |e verfasserin |4 aut | |
| 700 | 1 | |a Cavallini, Maria Cláudia Magalhães |e verfasserin |4 aut | |
| 700 | 1 | |a Rocha, Leonardo Silva |e verfasserin |4 aut | |
| 700 | 1 | |a Souza Peixoto, Albert |e verfasserin |4 aut | |
| 700 | 1 | |a Cugnasca, Beatriz S |e verfasserin |4 aut | |
| 700 | 1 | |a Cervi, Gustavo |e verfasserin |4 aut | |
| 700 | 1 | |a Correra, Thiago C |e verfasserin |4 aut | |
| 700 | 1 | |a Gonçalves, Augusto Cesar |e verfasserin |4 aut | |
| 700 | 1 | |a Festuccia, William Tadeu Lara |e verfasserin |4 aut | |
| 700 | 1 | |a Cunha, Thiago Mattar |e verfasserin |4 aut | |
| 700 | 1 | |a Yatsuda, Regiane |e verfasserin |4 aut | |
| 700 | 1 | |a de Magalhães, Amélia Cristina Mendes |e verfasserin |4 aut | |
| 700 | 1 | |a Dos Santos, Alcindo A |e verfasserin |4 aut | |
| 700 | 1 | |a Meotti, Flávia Carla |e verfasserin |4 aut | |
| 700 | 1 | |a Queiroz, Raphael Ferreira |e verfasserin |4 aut | |
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