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

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Abstract

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 < 0.01). Intestinal damage scores, anti-Zo-1 immunoreactivity H-score, serum FITC-Dextran levels, and bacterial translocation frequency (50% versus 100%) were significantly lower in the AP + LAR group compared to the AP group (all p < 0.01).

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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Funding

İnönü University Scientific Research Projects Unit: TCD-2022-2850 (30.05.2022).

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Authors and Affiliations

  1. Department of Internal Medicine, Malatya Turgut Özal University Faculty of Medicine, Malatya, Turkey

    Doğu Karahan

  2. Division of Gastroenterology, Department of Internal Medicine, İnönü University Faculty of Medicine, Malatya, Turkey

    Muhsin Murat Muhip Harputluoglu

  3. Department of Histology and Embryology, İnönü University Faculty of Medicine, Malatya, Turkey

    Mehmet Gul

  4. Department of Medical Microbiology, Malatya Turgut Özal University Faculty of Medicine, Malatya, Turkey

    Ayten Gunduz

  5. Department of Medical Biochemistry, Malatya Turgut Özal University Faculty of Medicine, Malatya, Turkey

    Fatma Ozyalin

  6. Department of Biostatistics, Malatya Turgut Özal University Faculty of Medicine, Malatya, Turkey

    Feyza İnceoğlu

  7. Department of General Surgery, Muğla Training and Research Hospital, Muğla, Turkey

    Deniz Tikici

  8. Department of Pharmacology, İnönü University Faculty of Pharmacy, Malatya, Turkey

    İsmet Yılmaz

  9. Department of Basic Pharmaceutical Sciences, İnönü University Faculty of Pharmacy, Malatya, Turkey

    Basri Satilmis

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  1. Doğu Karahan
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Correspondence to Doğu Karahan.

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Karahan, D., Harputluoglu, M.M.M., Gul, M. et al. Ameliorative Effects of Larazotide Acetate on Intestinal Permeability and Bacterial Translocation in Acute Pancreatitis Model in Rats. Dig Dis Sci 69, 1242–1252 (2024). https://doi.org/10.1007/s10620-024-08326-8

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  • DOI: https://doi.org/10.1007/s10620-024-08326-8

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