Novel potentials of the DPP-4 inhibitor sitagliptin against ischemia-reperfusion (I/R) injury in rat ex-vivo heart model

Amin Al-Awar, Nikoletta Almási, Renáta Szabó, Istvan Takacs, Zsolt Murlasits, Gergő Szűcs, Szilvia Török, Anikó Pósa, Csaba Varga, Krisztina Kupai

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral anti-diabetic drugs, implicated in pleiotropic secondary cardioprotective effects. The aim of the study was to unveil the unknown and possible cardioprotective targets that can be exerted by sitagliptin (Sitg) against ischemia-reperfusion (I/R) injury. Male wistar rats received 2 weeks’ Sitg oral treatment of different doses (25, 50, 100, and 150 mg/kg/day), or saline as a Control. Hearts were then isolated and subjected to two different I/R injury protocols: 10 min perfusion, 45 min regional ischemia, and 120 min reperfusion for infarct size (IS) measurement, or: 10 min perfusion, 45 min regional ischemia and 10 min reperfusion for biochemical analysis: nitric oxide synthases (NOSs) and DPP-4 activity, glucagon-like peptide-1 (GLP-1), Calcium, transient receptor potential vanilloid (TRPV)-1 and calcitonin gene-related peptide (CGRP) levels, transient receptor potential canonical (TRPC)-1 and e-NOS protein expression. NOS inhibitor (L-NAME) and TRPV-1 inhibitor (Capsazepine) were utilized to confirm the implication of both signaling mechanisms in DPP-4 inhibition-induced at the level of IS. Findings show that Sitg (50 mg) resulted in significant decrease in IS and DPP-4 activity, and significant increase in GLP-1, NOS activity, e-NOS expression, TRPV-1 level and TRPC-1 expression, compared to controls. Results of CGRP are in line with TRPV-1, as a downstream regulatory effect. NOS system and transient receptor potential (TRP) channels can contribute to DPP-4 inhibition-mediated cardioprotection against I/R injury using Sitagliptin.

Original languageEnglish
Article number3226
JournalInternational journal of molecular sciences
Volume19
Issue number10
DOIs
Publication statusPublished - Oct 18 2018

Keywords

  • Calcitonin gene related peptide
  • DPP-4 inhibitors
  • Dipeptidyl-peptidase-4
  • Endothelial nitric oxide synthase
  • Infarct size
  • Ischemia-reperfusion injury
  • NOS activity
  • Transient receptor potential channels

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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