Effects of Pituitary Adenylate Cyclase Activating Polypeptide in Human Proximal Tubule Cells Against Gentamicin Toxicity

  • G. HorvathEmail author
  • D. Reglodi
  • P. Czetany
  • A. Illes
  • Gy. Reman
  • A. Fekete
  • G. Toth
  • E. Laszlo
  • B. Opper
Short Communication


Nephrotoxicity by aminoglycoside antibiotics is a common cause of drug-induced nephropathy. Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide first isolated from hypothalamus, but later shown in widespread distribution. It exerts general cytoprotective effects in different cell types. Renoprotective effects of PACAP have been shown in various in vivo and in vitro experiments, but it is still not known whether it protects human proximal tubular cells against gentamicin toxicity. The aim of the present study was to investigate whether PACAP could influence the survival rate of human proximal tubular epithelial cells exposed to gentamicin treatment. For investigating its effect on cell survival after gentamicin treatment, cell viability was evaluated using MTT assay. Obtaining further insight into the background mechanism of gentamicin exposure and PACAP’s effect, expression of numerous kidney-related proteins was investigated using kidney biomarker array. Our results show that PACAP had protective effects against gentamicin-induced decreased cell viability, while it did not influence the proliferation activity of HK-2 cells. PACAP could counteract the expression-decreasing effect of gentamicin on dipeptidyl peptidase IV and vascular endothelial growth factor as assessed by kidney biomarker array. In summary, our present study could prove the protective effect of exogenous PACAP in gentamicin-induced nephrotoxicity.


HK-2 Pituitary adenylate cyclase activating polypeptide Cytoprotection Cell survival Aminoglycoside 



EFOP-3.6.1.-16-2016-00004, Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pecs/Centre for neuroscience, EFOP-3.6.2-16-2017-00008, “The role of neuro-inflammation in neurodegeneration: from molecules to clinics”, PTE AOK Research Grant KA-2016-03, KA-2017-17, OTKA (NKFIH) 115874 and 119759, 2017-1.2.1-NKP-2017-00002, Bolyai Scholarship, GINOP-2.3.2-15-2016-00050 “PEPSYS”, LP2011-08/2011, MTA-TKI 14016.

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest.

Human and Animal Rights

There were neither human nor animal experiments in our studies. Every experiment was done using cell line purchased from ATCC.

Informed Consent

Informed consent was not needed because of the in vitro nature of the investigations.


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Authors and Affiliations

  1. 1.Department of Anatomy, MTA-PTE PACAP Research Team, Centre for NeuroscienceUniversity of Pecs Medical SchoolPecsHungary
  2. 2.1st Department of Internal MedicineUniversity of Pecs Medical SchoolPecsHungary
  3. 3.1st Department of Pediatrics, MTA-SE Lendulet Diabetes Research TeamSemmelweis UniversityBudapestHungary
  4. 4.Medical ChemistryUniversity of SzegedSzegedHungary

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