Protective Effect of PACAP on Ischemia/Reperfusion-Induced Kidney Injury of Male and Female Rats: Gender Differences

Eszter Laszlo, Tamas Juhasz, Adam Varga, Bernadett Czibere, Krisztina Kovacs, Peter Degrell, Gabriella Horvath, Gabor Jancso, Peter Szakaly, A. Tamás, D. Reglodi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts general cytoprotective effects, including protection in different kidney disorders. The aim of our study was to investigate the ischemia/reperfusion-induced kidney injury of male and female rats to confirm the protective effects of PACAP in the kidney and to reveal possible gender differences. Male and female Wistar rats underwent unilateral renal artery clamping followed by 24-h, 48-h, or 14-day reperfusion. PACAP was administered intravenously before arterial clamping in half of the rats. Tubular damage, cytokine expression pattern, oxidative stress marker, antioxidative status and signaling pathways were evaluated using histology, immunohistology, cytokine array, PCR, and Western blot. Tubular damage was significantly less severe in the PACAP-treated male and female rats compared to controls. Results of female animals were significantly better in both treated and untreated groups. Cytokine expression, oxidative stress marker and antioxidative status confirmed the histological results. We also revealed that PACAP counteracted the decreased PKA phosphorylation, influenced the expression of BMP2 and BMP4, and increased the expression of the protein Smad1. We conclude that PACAP is protective in ischemia/reperfusion-induced kidney injury in both sexes, but females had markedly less pronounced injury after ischemia/reperfusion, possibly also involving further protective factors, the investigation of which could have future therapeutic value in treating ischemic kidney injuries.

Original languageEnglish
JournalJournal of Molecular Neuroscience
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Pituitary Adenylate Cyclase-Activating Polypeptide
Reperfusion
Ischemia
Kidney
Wounds and Injuries
Cytokines
Constriction
Smad1 Protein
Oxidative Stress
Renal Artery
Reperfusion Injury
Neuropeptides
Wistar Rats
Histology
Western Blotting
Phosphorylation
Polymerase Chain Reaction

Keywords

  • Bone morphogenetic protein
  • Cytokine expression
  • Ischemia/reperfusion
  • PACAP
  • Superoxide dismutase
  • Tubular damage

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Protective Effect of PACAP on Ischemia/Reperfusion-Induced Kidney Injury of Male and Female Rats : Gender Differences. / Laszlo, Eszter; Juhasz, Tamas; Varga, Adam; Czibere, Bernadett; Kovacs, Krisztina; Degrell, Peter; Horvath, Gabriella; Jancso, Gabor; Szakaly, Peter; Tamás, A.; Reglodi, D.

In: Journal of Molecular Neuroscience, 01.01.2018.

Research output: Contribution to journalArticle

Laszlo, Eszter ; Juhasz, Tamas ; Varga, Adam ; Czibere, Bernadett ; Kovacs, Krisztina ; Degrell, Peter ; Horvath, Gabriella ; Jancso, Gabor ; Szakaly, Peter ; Tamás, A. ; Reglodi, D. / Protective Effect of PACAP on Ischemia/Reperfusion-Induced Kidney Injury of Male and Female Rats : Gender Differences. In: Journal of Molecular Neuroscience. 2018.
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