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.
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Funding
This study was financially supported by the following: MTA-TKI 14016, EFOP-3.6.2-16-2017-00008 “The role of neuro-inflammation in neurodegeneration: from molecules to clinics”/Center for neuroscience, PTE AOK Research Grant KA-2017-17, NKFIH119759, 2017-1.2.1-NKP-2017-00002, Bolyai Scholarship, GINOP-2.3.2-15-2016-00050 “PEPSYS.” EFOP-3.6.1.-16-2016-00004—Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pécs, Higher Education Institutional Excellence Program of the Ministry of Human Capacities in Hungary, within the framework of the 20765-3/2018/FEKUTSTRAT. EFOP-3.6.3-VEKOP-16-2017-00009.
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Experimental procedures were carried out under approved protocols BA02/2000-24/2011.
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Laszlo, E., Juhasz, T., Varga, A. et al. Protective Effect of PACAP on Ischemia/Reperfusion-Induced Kidney Injury of Male and Female Rats: Gender Differences. J Mol Neurosci 68, 408–419 (2019). https://doi.org/10.1007/s12031-018-1207-y
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DOI: https://doi.org/10.1007/s12031-018-1207-y