Mechanism of preservation of the intestinal mucosa architecture and NF-κB/PGE2 reduction by hydrogen sulfide on cholera toxin-induced diarrhea in mice
| Autor: | André Luis Fernandes Lopes, Lucas A.D. Nicolau, Giovanny R. Pinto, Francisca Beatriz M. Sousa, Ana Patrícia de Oliveira, Hygor Ferreira-Fernandes, Jand V.R. Medeiros, Gabriella Pacheco |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Diarrhea
Male Cholera Toxin Morpholines Prostaglandin E2 receptor Crypt medicine.disease_cause Dinoprostone General Biochemistry Genetics and Molecular Biology Mice chemistry.chemical_compound Intestinal mucosa medicine Animals Hydrogen Sulfide Intestinal Mucosa General Pharmacology Toxicology and Pharmaceutics Prostaglandin E2 Receptor Chemistry Gene Expression Profiling Cholera toxin NF-kappa B Antagonist Organothiophosphorus Compounds NF-κB General Medicine Receptors Prostaglandin E EP2 Subtype Molecular biology Female Receptors Prostaglandin E EP4 Subtype medicine.drug |
| Zdroj: | Life Sciences. 284:119869 |
| ISSN: | 0024-3205 0441-8948 |
| DOI: | 10.1016/j.lfs.2021.119869 |
| Popis: | Aims Investigate the involvement of Hydrogen sulfide (H2S) in inflammatory parameters and intestinal morphology caused by cholera toxin (CT) in mice. Main methods Mice were subjected to the procedure of inducing diarrhea by CT in the isolated intestinal loop model. The intestinal loops were inoculated with H2S donor molecules (NaHS and GYY 4137) or saline and CT. To study the role of EP2 and EP4 prostaglandin E2 (PGE2) receptors in the H2S antisecretory effect, PAG (DL-propargylglycine - inhibitor of cystathionine-γ-lyase (CSE)), PF-04418948 (EP2 antagonist) and ONO-AE3-208 (EP4 antagonist) were used. The intestinal loops were evaluated for intestinal secretion, relation of the depth of villi and intestinal crypts, and real-time PCR for the mRNA of the CXCL2, IL-6, NOS-2, IL-17, NF-κB1, NF-κBIA, SLC6A4 and IFN-γ genes. Key findings H2S restored the villus/crypt depth ratio caused by CT. NaHS and GYY 4137 increased the expression of NF-κB1 and for the NF-κBIA gene, only GYY 4137 increased the expression of this gene. The increased expression of NF-κB inhibitors, NF-κB1 and NF-κBIA by H2S indicates a possible decrease in NF-κB activity. The pretreatment with PAG reversed the protective effect of PF-04418948 and ONO-AE3-208, indicating that H2S probably decreases PGE2 because in the presence of antagonists of this pathway, PAG promotes intestinal secretion. Significance Our results point to a protective activity of H2S against CT for promoting a protection of villus and crypt intestine morphology and also that its mechanism occurs at least in part due to decreasing the activity of NF-κB and PGE2. |
| Databáze: | OpenAIRE |
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