Effect of DPP-4 inhibitor sitagliptin against ischemia-reperfusion (I/R) injury in hyperlipidemic animals

Amin Al-Awar, Nikoletta Almási, Renáta Szabó, Rudolf Ménesi, Gergő Szűcs, Szilvia Török, A. Pósa, C. Varga, Krisztina Kupai

Research output: Contribution to journalArticle

Abstract

Hyperlipidemia is a major risk factor associated with increased risk of myocardial infarction. Dipeptidyl peptidase-4 (DPP-4) inhibitors such as sitagliptin are a class of oral anti-diabetic drugs with secondary pleiotropic effects on metabolic and cardiovascular parameters. This study aimed to determine the possible cardioprotective effects of sitagliptin on ischemia-reperfusion (I/R) injury in animals kept on high-fat diet. Male Wistar rats were fed with high-fat diet (HF) for 12 weeks, to induce hyperlipidemia. During the last two weeks of the feeding period, animals were orally treated with different doses of sitagliptin (Sitg: 25, 50, 100, and 150 mg/kg/day), or saline as a control. Heart tissues were then isolated and subjected to two different I/R-injury protocols for infarct size (IS) measurement and biochemical analysis. To test the role of NOS enzyme, NOS inhibitor (L-NAME) was injected intraperitoneally for IS evaluation. As an effective dose, Sitg (50 mg) exhibited a significant impact on IS. NOS activity increased significantly in the Sitg (50 mg) treated groups; however this protective effect was abolished in the presence of L-NAME. The protective effect of Sitg that was mediated by TRP channels in our previous study on normolipidemic animals was abrogated in animals fed with high-fat diet.

Original languageEnglish
Pages (from-to)180-189
Number of pages10
JournalActa Biologica Szegediensis
Volume62
Issue number2
DOIs
Publication statusPublished - Jan 1 2018

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Keywords

  • Dipeptidyl peptidase-4
  • DPP-4 inhibitors
  • Hyperlipidemia
  • Infarct size
  • Ischemia-reperfusion injury
  • NOS
  • TRP channels

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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