Preventive effects of guanosine on intestinal inflammation in 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats.
Animals
Anti-Inflammatory Agents
/ pharmacology
Antioxidants
/ pharmacology
Colitis
/ chemically induced
Colon
/ drug effects
Cytokines
/ metabolism
Dinitrofluorobenzene
/ analogs & derivatives
Guanosine
/ pharmacology
Inflammation
/ chemically induced
Interleukin-1beta
/ metabolism
Interleukin-6
/ metabolism
Intestinal Mucosa
/ drug effects
NF-kappa B
Rats
Rats, Wistar
Reactive Oxygen Species
/ metabolism
Tumor Necrosis Factor-alpha
/ metabolism
DNBS rat
Guanosine
Inflammatory bowel disease
Purines
Journal
Inflammopharmacology
ISSN: 1568-5608
Titre abrégé: Inflammopharmacology
Pays: Switzerland
ID NLM: 9112626
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
28
03
2018
accepted:
06
06
2018
pubmed:
17
6
2018
medline:
27
8
2019
entrez:
17
6
2018
Statut:
ppublish
Résumé
Guanosine, a guanine-based purine, is an extracellular signaling molecule exerting anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. We aimed to investigate its protective effects on 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rat. Rats were divided into five groups and colitis was induced by intracolonic instillation of DNBS (15 mg/rat). Guanosine (4 or 8 mg/kg) was administered for 6 days i.p. starting the day of the colitis induction. Body weight loss, stool consistency, colon weight/length, histological analysis, myeloperoxidase activity (MPO) and pro-inflammatory cytokine levels were assessed. Immunoblotting of nuclear factor-κB (NF-κB) p65 protein levels and detection of oxidative and nitrosative stress markers were also performed. Guanosine, in a dose-dependent manner, significantly ameliorated the severity of DNBS-induced colitis, reducing body weight loss and diarrhea incidence, preventing the DNBS-induced macroscopic and microscopic damage to the colonic mucosa, and the MPO increase. Guanosine treatment also lowered interleukin-1β, interleukin-6, and tumor necrosis factor-α mRNA levels. Importantly, guanosine in DNBS rats down-regulated the expression of NF-κB p65 and the levels of reactive oxygen species and nitrite. In conclusion, guanosine exerts beneficial effects in DNBS-induced colitis in rats, through modulation of colonic inflammation, downregulating of NFκB-mediated signaling.
Sections du résumé
BACKGROUND
BACKGROUND
Guanosine, a guanine-based purine, is an extracellular signaling molecule exerting anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. We aimed to investigate its protective effects on 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rat.
METHODS
METHODS
Rats were divided into five groups and colitis was induced by intracolonic instillation of DNBS (15 mg/rat). Guanosine (4 or 8 mg/kg) was administered for 6 days i.p. starting the day of the colitis induction. Body weight loss, stool consistency, colon weight/length, histological analysis, myeloperoxidase activity (MPO) and pro-inflammatory cytokine levels were assessed. Immunoblotting of nuclear factor-κB (NF-κB) p65 protein levels and detection of oxidative and nitrosative stress markers were also performed.
RESULTS
RESULTS
Guanosine, in a dose-dependent manner, significantly ameliorated the severity of DNBS-induced colitis, reducing body weight loss and diarrhea incidence, preventing the DNBS-induced macroscopic and microscopic damage to the colonic mucosa, and the MPO increase. Guanosine treatment also lowered interleukin-1β, interleukin-6, and tumor necrosis factor-α mRNA levels. Importantly, guanosine in DNBS rats down-regulated the expression of NF-κB p65 and the levels of reactive oxygen species and nitrite.
CONCLUSIONS
CONCLUSIONS
In conclusion, guanosine exerts beneficial effects in DNBS-induced colitis in rats, through modulation of colonic inflammation, downregulating of NFκB-mediated signaling.
Identifiants
pubmed: 29907915
doi: 10.1007/s10787-018-0506-9
pii: 10.1007/s10787-018-0506-9
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Antioxidants
0
Cytokines
0
Interleukin-1beta
0
Interleukin-6
0
NF-kappa B
0
Reactive Oxygen Species
0
Tumor Necrosis Factor-alpha
0
Guanosine
12133JR80S
2,4-dinitrofluorobenzene sulfonic acid
143134-35-4
Dinitrofluorobenzene
D241E059U6
Types de publication
Journal Article
Langues
eng
Pagination
349-359Subventions
Organisme : Università degli Studi di Palermo
ID : FFR 2012/13
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