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Comparison of Intestinal Warm Ischemic Injury in PACAP Knockout and Wild-Type Mice

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Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in the gastrointestinal tract and plays a central role in the intestinal physiology, mainly in the secretion and motility. The aim of our study was to compare the ischemic injury in wild-type and PACAP-38 knockout mice following warm mesenteric small bowel ischemia. Warm ischemia groups were designed with occlusion of superior mesenteric artery for 1, 3, and 6 h in wild-type (n = 10 in each group) and PACAP-38 knockout (n = 10 in each group) mice. Small bowel biopsies were collected after laparotomy (control) and at the end of the ischemia periods. To determine oxidative stress parameters, malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) were measured. Tissue damage was analyzed by qualitative and quantitative methods on hematoxylin/eosin-stained sections. In PACAP-38 knockout animals, tissue MDA increased significantly after 3 and 6 h ischemia (133.97 ± 6,2; 141.86 ± 5,8) compared to sham-operated (100.92 ± 3,6) and compared to wild-type results (112.8 ± 2,1; 118.4 ± 1.03 μmol/g, p < 0.05). Meanwhile, tissue concentration of GSH and activity of SOD decreased significantly in knockout mice compared to wild-type form (GSH, 795.97 ± 10.4; 665.1 ± 8,8 vs. 893.23 ± μmol/g; SOD, 94.4 ± 1.4; 81.2 ± 3.9 vs. 208.09 ± 3,7 IU/g). Qualitative and quantitative histological results showed destruction of the mucous, submucous layers, and crypts in knockout mice compared to wild-type tissues. These processes correlated with the warm ischemia periods. Our present results propose an important protective effect of endogenous PACAP-38 against intestinal warm ischemia, which provides basis for further investigation to elucidate the mechanism of this protective effect.

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Acknowledgements

This study was supported by Hungarian Scientific Research Fund (Grant OTKA PD77474, K72592, K73044, and CNK78480), ETT278-04/2009, Bolyai Scholarship of the Hungarian Academy of Sciences, and Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Department of Surgical Research and Techniques, University of Pecs Medical School, Kodaly Zoltan Street 20, 7624, Pecs, Hungary

    Andrea Ferencz & Gyorgy Weber

  2. Department of Anatomy, University of Pecs Medical School, Kodaly Zoltan Street 20, 7624, Pecs, Hungary

    Peter Kiss & Dora Reglodi

  3. Department of Pharmacology and Pharmacotherapy, University of Pecs Medical School, Kodaly Zoltan Street 20, 7624, Pecs, Hungary

    Zsuzsanna Helyes

  4. Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

    Norihito Shintani & Akemichi Baba

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  1. Andrea Ferencz
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  2. Peter Kiss
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  4. Zsuzsanna Helyes
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  5. Norihito Shintani
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Correspondence to Andrea Ferencz.

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Ferencz, A., Kiss, P., Weber, G. et al. Comparison of Intestinal Warm Ischemic Injury in PACAP Knockout and Wild-Type Mice. J Mol Neurosci 42, 435–442 (2010). https://doi.org/10.1007/s12031-010-9357-6

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  • DOI: https://doi.org/10.1007/s12031-010-9357-6

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