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Quercetin protects against intestinal barrier disruption and inflammation in acute necrotizing pancreatitis through TLR4/MyD88/p38 MAPK and ERS inhibition
- Source :
- Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 18(7)
- Publication Year :
- 2018
-
Abstract
- To investigate the effects of quercetin on intestinal barrier disruption and inflammation in acute necrotizing pancreatitis (ANP) in rats, and its possible mechanism.ANP was established by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, and quercetin (50 mg/kg × 3) was administered by intraperitoneal injection prior to and after ANP induction. Pancreatitis was assessed by pancreatic histopathology, plasma amylase, pancreatic myeloperoxidase (MPO) activity, IL-1β, TNFα and IL-6 levels. Injury of the distal ileum was assessed by histological evaluation. The ultrastructural changes of ileal epithelial cells were examined by transmission electron microscope (TEM). Intestinal barrier function was estimated by plasma diamine oxidase (DAO), d-lactate, endotoxin; and intestinal tight junction proteins including zonula occludens-1 (ZO-1), claudin 1, occludin; and bacterial translocation. Intestinal inflammation was determined by IL-1β, TNFα and IL-17 A expression. TLR4, MyD88, pp38 MAPK, and endoplasmic reticulum stress (ERS)-related molecules (Bip, p-IRE1α, sXBP1, p-eIF2α, ATF6) were measured by immunohistochemistry and WB.Quercetin intervention attenuated pancreatic and ileal pathological damages in ANP (P 0.05), ameliorated intestinal barrier disruption and inflammation (P 0.05). Meantime, QE significantly suppressed intestinal TLR4/MyD88/p38 MAPK pathway and ERS activation.Quercetin plays a protective role against intestinal barrier disruption and inflammation in ANP, probably partly by inhibiting TLR4/MyD88/p38 MAPK and ERS activation.
- Subjects :
- 0301 basic medicine
Taurocholic Acid
Endocrinology, Diabetes and Metabolism
Ileum
Inflammation
Pharmacology
Occludin
p38 Mitogen-Activated Protein Kinases
03 medical and health sciences
medicine
Humans
Claudin
Barrier function
Hepatology
biology
business.industry
Pancreatitis, Acute Necrotizing
Gastroenterology
medicine.disease
Endoplasmic Reticulum Stress
Intestines
Toll-Like Receptor 4
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
Myeloperoxidase
Myeloid Differentiation Factor 88
biology.protein
Pancreatitis
Tumor necrosis factor alpha
Quercetin
medicine.symptom
business
Subjects
Details
- ISSN :
- 14243911
- Volume :
- 18
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
- Accession number :
- edsair.doi.dedup.....4b608c1b0f225aee2f871c611c24a038