Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis
| Autor: | Radhakrishna Rao, Joseph F. Pierre, Avtar S. Meena, Cherie Canelas, Geetha Samak, Kesha Dalal, Pradeep K. Shukla |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Colon Science Anti-Inflammatory Agents Gut flora Systemic inflammation Article Proinflammatory cytokine Tight Junctions chemistry.chemical_compound Mice Corticosterone Stress Physiological Internal medicine medicine Animals Humans Chronic stress Gastrointestinal models Liver Diseases Alcoholic Neuroinflammation Inflammation Multidisciplinary biology Tight junction Ethanol business.industry Central Nervous System Depressants Drug Synergism biology.organism_classification Gastrointestinal Tract Mice Inbred C57BL Disease Models Animal Endocrinology chemistry Brain Injuries Cytokines Medicine Female medicine.symptom business Hormone |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-18 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Alcohol use disorders are associated with altered stress responses, but the impact of stress or stress hormones on alcohol-associated tissue injury remain unknown. We evaluated the effects of chronic restraint stress on alcohol-induced gut barrier dysfunction and liver damage in mice. To determine whether corticosterone is the stress hormone associated with the stress-induced effects, we evaluated the effect of chronic corticosterone treatment on alcoholic tissue injury at the Gut-Liver-Brain (GLB) axis. Chronic restraint stress synergized alcohol-induced epithelial tight junction disruption and mucosal barrier dysfunction in the mouse intestine. These effects of stress on the gut were reproduced by corticosterone treatment. Corticosterone synergized alcohol-induced expression of inflammatory cytokines and chemokines in the colonic mucosa, and it potentiated the alcohol-induced endotoxemia and systemic inflammation. Corticosterone also potentiated alcohol-induced liver damage and neuroinflammation. Metagenomic analyses of 16S RNA from fecal samples indicated that corticosterone modulates alcohol-induced changes in the diversity and abundance of gut microbiota. In Caco-2 cell monolayers, corticosterone dose-dependently potentiated ethanol and acetaldehyde-induced tight junction disruption and barrier dysfunction. These data indicate that chronic stress and corticosterone exacerbate alcohol-induced mucosal barrier dysfunction, endotoxemia, and systemic alcohol responses. Corticosterone-mediated promotion of alcohol-induced intestinal epithelial barrier dysfunction and modulation of gut microbiota may play a crucial role in the mechanism of stress-induced promotion of alcohol-associated tissue injury at the GLB axis. |
| Databáze: | OpenAIRE |
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