Effect of N-Acetylserotonin on TLR-4 and MyD88 Expression during Intestinal Ischemia-Reperfusion in a Rat Model.
Animals
Apoptosis
/ drug effects
Biomarkers
/ metabolism
Blotting, Western
Down-Regulation
Immunohistochemistry
Intestinal Mucosa
/ drug effects
Intestine, Small
/ drug effects
Male
Myeloid Differentiation Factor 88
/ metabolism
Polymerase Chain Reaction
Random Allocation
Rats
Rats, Sprague-Dawley
Reperfusion Injury
/ metabolism
Serotonin
/ analogs & derivatives
TNF Receptor-Associated Factor 6
/ metabolism
Toll-Like Receptor 4
/ metabolism
Up-Regulation
Journal
European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie
ISSN: 1439-359X
Titre abrégé: Eur J Pediatr Surg
Pays: United States
ID NLM: 9105263
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
pubmed:
6
1
2018
medline:
4
4
2019
entrez:
6
1
2018
Statut:
ppublish
Résumé
Accumulating evidence indicates that changes in intestinal toll-like receptors (TLRs) precede histological injury in a rodent model of necrotizing enterocolitis. N-acetylserotonin (NAS) is a naturally occurring chemical intermediate in the biosynthesis of melatonin. A recent study has shown that treatment with NAS prevents gut mucosal damage and inhibits programmed cell death following intestinal ischemia-reperfusion (IR). The objective of this study was to determine the effects of NAS on TLR-4, myeloid differentiation factor 88 (Myd88), and TNF-α receptor-associated factor 6 (TRAF6) expression in intestinal mucosa following intestinal IR in a rat. Male Sprague-Dawley rats were randomly assigned to one of the four experimental groups: 1) Sham rats underwent laparotomy; 2) Sham-NAS rats underwent laparotomy and were treated with intraperitoneal (IP) NAS (20 mg/kg); 3) IR rats underwent occlusion of both superior mesenteric artery and portal vein for 20 minutes followed by 48 hours of reperfusion; and 4) IR-NAS rats underwent IR and were treated with IP NAS immediately before abdominal closure. Intestinal structural changes, mucosal TLR-4, MyD88, and TRAF6 mucosal gene, and protein expression were examined using real-time PCR, Western blot, and immunohistochemistry. Significant mucosal damage in IR rats was accompanied by a significant upregulation of TLR-4, MyD88, and TRAF6 gene and protein expression in intestinal mucosa compared with control animals. The administration of NAS decreased the intestinal injury score, inhibited cell apoptosis, and significantly reduced the expression of TLR-4, MyD88, and TRAF6. Treatment with NAS is associated with downregulation of TLR-4, MyD88, and TRAF6 expression along with a concomitant decrease in intestinal mucosal injury caused by intestinal IR in a rat.
Sections du résumé
BACKGROUND
BACKGROUND
Accumulating evidence indicates that changes in intestinal toll-like receptors (TLRs) precede histological injury in a rodent model of necrotizing enterocolitis. N-acetylserotonin (NAS) is a naturally occurring chemical intermediate in the biosynthesis of melatonin. A recent study has shown that treatment with NAS prevents gut mucosal damage and inhibits programmed cell death following intestinal ischemia-reperfusion (IR). The objective of this study was to determine the effects of NAS on TLR-4, myeloid differentiation factor 88 (Myd88), and TNF-α receptor-associated factor 6 (TRAF6) expression in intestinal mucosa following intestinal IR in a rat.
MATERIALS AND METHODS
METHODS
Male Sprague-Dawley rats were randomly assigned to one of the four experimental groups: 1) Sham rats underwent laparotomy; 2) Sham-NAS rats underwent laparotomy and were treated with intraperitoneal (IP) NAS (20 mg/kg); 3) IR rats underwent occlusion of both superior mesenteric artery and portal vein for 20 minutes followed by 48 hours of reperfusion; and 4) IR-NAS rats underwent IR and were treated with IP NAS immediately before abdominal closure. Intestinal structural changes, mucosal TLR-4, MyD88, and TRAF6 mucosal gene, and protein expression were examined using real-time PCR, Western blot, and immunohistochemistry.
RESULTS
RESULTS
Significant mucosal damage in IR rats was accompanied by a significant upregulation of TLR-4, MyD88, and TRAF6 gene and protein expression in intestinal mucosa compared with control animals. The administration of NAS decreased the intestinal injury score, inhibited cell apoptosis, and significantly reduced the expression of TLR-4, MyD88, and TRAF6.
CONCLUSION
CONCLUSIONS
Treatment with NAS is associated with downregulation of TLR-4, MyD88, and TRAF6 expression along with a concomitant decrease in intestinal mucosal injury caused by intestinal IR in a rat.
Identifiants
pubmed: 29304519
doi: 10.1055/s-0037-1618593
doi:
Substances chimiques
Biomarkers
0
Myd88 protein, rat
0
Myeloid Differentiation Factor 88
0
TNF Receptor-Associated Factor 6
0
Tlr4 protein, rat
0
Toll-Like Receptor 4
0
Serotonin
333DO1RDJY
N-acetylserotonin
P4TO3C82WV
Types de publication
Evaluation Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
188-195Informations de copyright
Georg Thieme Verlag KG Stuttgart · New York.
Déclaration de conflit d'intérêts
None.