Sodium Butyrate Protects Against Intestinal Oxidative Damage and Neuroinflammation in the Prefrontal Cortex of Ulcerative Colitis Mice Model.

Autor: Silveira AK; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Federal University of Rio Grande Do Sul (UFRGS) Avenida, Porto Alegre, Brazil., Gomes HM; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Federal University of Rio Grande Do Sul (UFRGS) Avenida, Porto Alegre, Brazil., Fröhlich NT; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Federal University of Rio Grande Do Sul (UFRGS) Avenida, Porto Alegre, Brazil., Possa L; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Federal University of Rio Grande Do Sul (UFRGS) Avenida, Porto Alegre, Brazil., Santos L; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Federal University of Rio Grande Do Sul (UFRGS) Avenida, Porto Alegre, Brazil., Kessler F; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Federal University of Rio Grande Do Sul (UFRGS) Avenida, Porto Alegre, Brazil., Martins A; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Federal University of Rio Grande Do Sul (UFRGS) Avenida, Porto Alegre, Brazil., Rodrigues MS; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Federal University of Rio Grande Do Sul (UFRGS) Avenida, Porto Alegre, Brazil., De Oliveira J; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Federal University of Rio Grande Do Sul (UFRGS) Avenida, Porto Alegre, Brazil., do Nascimento ND; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Federal University of Rio Grande Do Sul (UFRGS) Avenida, Porto Alegre, Brazil., Sirena D; Hospital de Clinicas de Porto Alegre (HCPA), Clinics Hospital of Porto Alegre, Porto Alegre, Brazil., Paz AH; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Federal University of Rio Grande Do Sul (UFRGS) Avenida, Porto Alegre, Brazil., Gelain DP; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Federal University of Rio Grande Do Sul (UFRGS) Avenida, Porto Alegre, Brazil., Moreira JCF; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Federal University of Rio Grande Do Sul (UFRGS) Avenida, Porto Alegre, Brazil.
Jazyk: angličtina
Zdroj: Immunological investigations [Immunol Invest] 2023 Nov; Vol. 52 (7), pp. 796-814. Date of Electronic Publication: 2023 Sep 04.
DOI: 10.1080/08820139.2023.2244967
Abstrakt: Inflammatory bowel diseases (IBD) cause increased inflammatory signalling and oxidative damage. IBDs are correlated with an increased incidence of brain-related disorders suggesting that the gut-brain-axis exerts a pivotal role in IBD. Butyrate is one of the main microbial metabolites in the colon, and it can cross the blood-brain barrier, directly affecting the brain. We induced ulcerative colitis (UC) in mice utilizing dextran sodium sulfate (DSS) in the drinking water for 7 days. Animals were divided into four groups, receiving water or DSS and treated with saline or 0,066 g/kg of Sodium Butyrate for 7 days. We also used an integrative approach, combining bioinformatics functional network and experimental strategies to understand how butyrate may affect UC. Butyrate was able to attenuate colitis severity and intestinal inflammation. Butyrate protected the colon against oxidative damage in UC and protected the prefrontal cortex from neuroinflammation observed in DSS group. Immunocontent of tight junction proteins Claudin-5 and Occludin were reduced in colon of DSS group mice and butyrate was able to restore to control levels. Occludin and Claudin-5 decrease in DSS group indicate that an intestinal barrier disruption may lead to the increased influx of gut-derived molecules, causing neuroinflammation in the prefrontal cortex, observed by increased IBA-1 marker. The probable protection mechanism of butyrate treatment occurs through NRF2 through Nrf2 and HIF-1α activation and consequent activation of catalase and superoxide dismutase. Our data suggest that systemic inflammation associated with intestinal barrier disruption in UC leads to neuroinflammation in the prefrontal cortex, which was atenuated by butyrate.
Databáze: MEDLINE
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