Effect of N-Acetylserotonin on TLR-4 and MyD88 Expression during Intestinal Ischemia-Reperfusion in a Rat Model
| Autor: | Yoav Ben Shahar, Salim Halabi, Yulia Pollak, Arnold G. Coran, Tatiana Dorfman, Nir Bitterman, Arie Bitterman, Igor Sukhotnik |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Serotonin medicine.medical_specialty Programmed cell death Blotting Western Down-Regulation Apoptosis Polymerase Chain Reaction Rats Sprague-Dawley Random Allocation 03 medical and health sciences chemistry.chemical_compound Downregulation and upregulation Intestinal mucosa Western blot Internal medicine N-Acetylserotonin medicine.artery Intestine Small medicine Animals Superior mesenteric artery Intestinal Mucosa Receptor TNF Receptor-Associated Factor 6 medicine.diagnostic_test business.industry Immunohistochemistry Rats Up-Regulation Toll-Like Receptor 4 030104 developmental biology Endocrinology chemistry Reperfusion Injury Myeloid Differentiation Factor 88 Pediatrics Perinatology and Child Health Surgery business Biomarkers |
| Zdroj: | European Journal of Pediatric Surgery. 29:188-195 |
| ISSN: | 1439-359X 0939-7248 |
| Popis: | 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 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 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 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. |
| Databáze: | OpenAIRE |
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