Effect of N-Acetylserotonin on TLR-4 and MyD88 Expression during Intestinal Ischemia-Reperfusion in a Rat Model

2018 ◽  
Vol 29 (02) ◽  
pp. 188-195 ◽  
Author(s):  
Yoav Ben Shahar ◽  
Salim Halabi ◽  
Nir Bitterman ◽  
Tatiana Dorfman ◽  
Yulia Pollak ◽  
...  
Keyword(s):  
Protein Expression ◽  
Intestinal Mucosa ◽  
Intestinal Ischemia ◽  
Structural Changes ◽  
Ischemia Reperfusion ◽  
Mucosal Injury ◽  
Mucosal Damage ◽  
Sprague Dawley ◽  
Gene And Protein Expression ◽  
Intestinal Ischemia Reperfusion

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.

The role of leukocytes in mediating mucosal injury of intestinal ischemia/reperfusion

1990 ◽  
Vol 25 (2) ◽  
pp. 214-217 ◽  
Author(s):  
Mark F. Brown ◽  
Arthur J. Ross ◽  
James Dasher ◽  
Debra L. Turley ◽  
Moritz M. Ziegler ◽  
...  
Keyword(s):  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Mucosal Injury ◽  
Intestinal Ischemia Reperfusion

The Effect ofGinkgo bilobaExtract (EGb 761) Pretreatment on Intestinal Epithelial Apoptosis Induced by Intestinal Ischemia/Reperfusion in Rats: Role of Ceramide

2007 ◽  
Vol 35 (05) ◽  
pp. 805-819 ◽  
Author(s):  
Ke-Xuan Liu ◽  
Wei He ◽  
Timo Rinne ◽  
Ying Liu ◽  
Ming-Qi Zhao ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Mrna Expression ◽  
Intestinal Mucosa ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Intestinal Epithelial ◽  
Egb 761 ◽  
Major Mode ◽  
Intestinal Ischemia Reperfusion ◽  
Ceramide Generation

Apoptosis was demonstrated to be a major mode of intestinal epithelial cell death caused by intestinal ischemia/reperfusion ( II / R ). Ceramide has been proposed as a messenger for apoptosis. The present study was aimed to investigate the effect of Ginkgo biloba extract 761 (EGb 761) pretreatment on II / R -induced intestinal mucosal epithelial apoptosis in rats and the mechanism related to ceramide. The rat model of II / R injury was produced by clamping superior mesenteric artery for 60 min followed by reperfusion for 180 min. Twenty four rats were randomly allocated into Sham, II / R and EGb + II / R groups. In EGb + II / R group, EGb 761 (100 mg/kg per day) was administered intragastrically for 7 days before the surgery. Animals in II / R and sham groups were treated with equal volume of normal saline solution. Intestinal mucosal epithelial apoptosis was detected via electron microscopy and TUNEL method. Lipid peroxidation in intestinal mucosa was determined by detecting the malondialdehyde level and the activities of superoxide dismutase and peroxidase glutathione. The ceramide generation and sphingomyelinase (SMase) mRNA expression in intestinal mucosa were determined by high performance, thin layer chromatography, and RT-PCR, respectively. II / R caused intestinal mucosal epithelial apoptosis and over-production of the ceramide accompanied by up-regulation of SMase mRNA expression and increases of lipid peroxidation. EGb 761 pretreatment significantly decreased apoptosis index, and concurrently reduced the ceramide generation accompanied by down-regulation of SMase expression and inhibition of lipid peroxidation. The findings indicate that EGb 761 pretreatment attenuates II / R -induced intestinal epithelial apoptosis, which might be attributable to its antioxidant action of mediating ceramide pathway.

scholarly journals Antioxidant-Based Therapy Reduces Early-Stage Intestinal Ischemia-Reperfusion Injury in Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 853
Author(s):  
Gaizka Gutiérrez-Sánchez ◽  
Ignacio García-Alonso ◽  
Jorge Gutiérrez Sáenz de Santa María ◽  
Ana Alonso-Varona ◽  
Borja Herrero de la Parte
Keyword(s):  
Reperfusion Injury ◽  
Intestinal Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Early Stage ◽  
Ischemia Reperfusion ◽  
Mucosal Damage ◽  
Intestinal Damage ◽  
Oxygen Species ◽  
Intestinal Ischemia Reperfusion

Intestinal ischemia-reperfusion injury (i-IRI) is a rare disorder with a high mortality rate, resulting from the loss of blood flow to an intestinal segment. Most of the damage is triggered by the restoration of flow and the arrival of cytokines and reactive oxygen species (ROS), among others. Inactivation of these molecules before tissue reperfusion could reduce intestinal damage. The aim of this work was to analyze the preventive effect of allopurinol and nitroindazole on intestinal mucosal damage after i-IRI. Wag/RijHsd rats were subjected to i-IRI by clamping the superior mesenteric artery (for 1 or 2 h) followed by a 30 min period of reperfusion. Histopathological intestinal damage (HID) was assessed by microscopic examination of histological sections obtained from injured intestine. HID was increased by almost 20% by doubling the ischemia time (from 1 to 2 h). Nitroindazole reduced HID in both the 1 and 2 h period of ischemia by approximately 30% and 60%, respectively (p < 0.001). Our preliminary results demonstrate that nitroindazole has a preventive/protective effect against tissue damage in the early stages of i-IRI. However, to better understand the molecular mechanisms underlying this phenomenon, further studies are needed.

Sign in / Sign up

Export Citation Format

Share Document