Ameliorative Effects of Larazotide Acetate on Intestinal Permeability and Bacterial Translocation in Acute Pancreatitis Model in Rats.
This rat study investigated whether larazotide acetate (LA), a tight junction regulator that blocks zonulin receptors in the intestinal epithelium, could reduce intestinal barrier dysfunction and bacterial translocation in an experimentally induced acute pancreatitis (AP) model. Thirty-two male Sprague-Dawley rats were divided into four groups (control, larazotide-only, AP, and AP + larazotide). AP was induced via intraperitoneal L-Arginine injections, and LA was administered orally for seven days prior to AP induction. Intestinal permeability was assessed using FITC-Dextran, bacterial translocation was evaluated by culturing samples from liver, mesentery, and spleen, and intestinal histopathology including zonulin-1 (ZO-1) immunoreactivity was analyzed. The study found that, compared to the AP-only group, the AP + LA group showed significantly reduced intestinal damage scores, lower serum FITC-Dextran levels, decreased ZO-1 immunoreactivity, and a lower frequency of bacterial translocation. Key limitations include the exclusive use of an animal model, a small sample size, a single AP-induction method (L-Arginine), and a prophylactic rather than therapeutic administration design, which may limit clinical translatability.
Why this grade: The study was conducted entirely in rats (n=32) with no human subjects, providing no direct human evidence for the effects of larazotide acetate on acute pancreatitis-related intestinal dysfunction.
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 Conclusions Our findings show that LA reduces the increased intestinal permeability and intestinal damage by its effect on Zo in the AP model in rats, and decreases the frequency of bacterial translocation as a result of these positive effects.
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