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Effects of PACAP on Survival and Renal Morphology in Rats Subjected to Renal Ischemia/Reperfusion

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Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) occurs and exerts a variety of biological functions in the nervous system and in the peripheral organs, including the urinary system. PACAP has protective effects against myeloma kidney injury and renal ischemia. Ischemia/reperfusion injury of the kidney is a major clinical problem, and based on the protective effects of PACAP in cerebral and cardiomyocyte ischemia, the aim of the present study was to evaluate the effects of a single intravenous PACAP injection on the survival and renal morphology after varying times of ischemia. Rats were subjected to renal artery clamping for 15, 30, 45, 60, or 75 min followed by reperfusion. PACAP (100 μg) was administered intravenously before arterial clamping. We found that a 15- or 30-min renal ischemia led to no renal dysfunction, and the kidneys showed normal appearance with no difference between PACAP- and saline-treated groups. Control rats with 45 min of ischemia had increased premature death rate and showed multifocal acute tubular atrophy, while a 60-min ischemia led to death of all control animals within a few days displaying severe, multifocal Grade II tubular atrophy. In contrast, all PACAP-treated animals survived with subtle morphological changes after the 45-min ischemia. After the 60-min ischemia, death rate was significantly lower in PACAP-treated rats compared to controls, and animals showed subtle focal tubular alteration. A 75-min ischemia was not performable in controls because of deaths before the termination of ischemia. PACAP-treated rats survived longer, but they also died after 5–10 days exhibiting severe focal tubular atrophy. In summary, our results clearly show that PACAP is able to prolong the renal ischemic time, decrease mortality, and attenuate tubular degeneration after renal ischemia.

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Acknowledgments

This work was supported by the Hungarian Science Research Fund (OTKA T046589, F 67830, K72592 and F 048908), MEDIPOLIS Pecs and ETT439/2006.

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Authors and Affiliations

  1. Department of Surgery, University of Pecs, Pecs, Hungary

    Peter Szakaly

  2. Department of Anatomy, University of Pecs, Szigeti u 12, 7624, Pecs, Hungary

    Peter Kiss, Andrea Lubics, Andrea Tamas, Istvan Lengvari & Dora Reglodi

  3. Department of Laboratory Medicine, University of Pecs, Pecs, Hungary

    Tamas Magyarlaki

  4. Department of Surgical Research and Techniques, University of Pecs, Pecs, Hungary

    Boglarka Racz

  5. Department of Medical Chemistry, University of Szeged, Szeged, Hungary

    Gabor Toth

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  1. Peter Szakaly
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  2. Peter Kiss
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  3. Andrea Lubics
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Correspondence to Dora Reglodi.

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Szakaly, P., Kiss, P., Lubics, A. et al. Effects of PACAP on Survival and Renal Morphology in Rats Subjected to Renal Ischemia/Reperfusion. J Mol Neurosci 36, 89–96 (2008). https://doi.org/10.1007/s12031-008-9064-8

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