Ameliorative Effects of Larazotide Acetate on Intestinal Permeability and Bacterial Translocation in Acute Pancreatitis Model in Rats

Background Intestinal barrier dysfunction in acute pancreatitis (AP) may progress to systemic inflammatory response syndrome (SIRS) and multi-organ failures by causing bacterial translocation. Larazotide acetate (LA) is a molecule that acts as a tight junction (TJ) regulator by blocking zonulin (Zo)...

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Published in:Digestive diseases and sciences 2024-04, Vol.69 (4), p.1242-1252
Main Authors: Karahan, Doğu, Harputluoglu, Muhsin Murat Muhip, Gul, Mehmet, Gunduz, Ayten, Ozyalin, Fatma, İnceoğlu, Feyza, Tikici, Deniz, Yılmaz, İsmet, Satilmis, Basri
Format: Article
Language:English
Subjects:
Acute Disease
Animals
Arginine
Bacterial Translocation
Biochemistry
Dextrans
Fluorescein-5-isothiocyanate - analogs & derivatives
Gastroenterology
Hepatology
Intestinal Barrier Function
Intestinal Diseases - metabolism
Intestinal Mucosa - metabolism
Male
Medicine
Medicine & Public Health
Oligopeptides - pharmacology
Oncology
Original Article
Pancreatitis
Pancreatitis - metabolism
Permeability
Rats
Rats, Sprague-Dawley
Transplant Surgery
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Summary:Background Intestinal barrier dysfunction in acute pancreatitis (AP) may progress to systemic inflammatory response syndrome (SIRS) and multi-organ failures by causing bacterial translocation. Larazotide acetate (LA) is a molecule that acts as a tight junction (TJ) regulator by blocking zonulin (Zo) receptors in the intestine. Aims In our study, we aimed to investigate the effects of LA on intestinal barrier dysfunction and bacterial translocation in the AP model in rats. Methods Thirty-two male Sprague-Dawley rats were divided into 4 groups; control, larazotide (LAR), AP, and AP + LAR. The AP model was created by administering 250 mg/100 g bm l -Arginine intraperitoneally 2 times with an hour interval. AP + LAR group received prophylactic 0.01 mg/mL LA orally for 7 days before the first dose of l -Arginine. For intestinal permeability analysis, fluorescein isothiocyanate-dextran (FITC-Dextran) was applied to rats by gavage. The positivity of any of the liver, small intestine mesentery, and spleen cultures were defined as bacterial translocation. Histopathologically damage and zonulin immunoreactivity in the intestine were investigated. Results Compared to the control group, the intestinal damage scores, anti-Zo-1 immunoreactivity H-Score, serum FITC-Dextran levels and bacterial translocation frequency (100% versus 0%) in the AP group were significantly higher (all p  
ISSN:0163-2116
1573-2568
DOI:10.1007/s10620-024-08326-8