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; Anikó Pósa; Csaba Varga; Krisztina Kupai

doi:10.14232/abs.2018.2.180-189

Authors

Amin Al-awar
Nikoletta Almási https://orcid.org/0000-0002-7371-5272
Renáta Szabó
Rudolf Ménesi
Gergő Szűcs
Szilvia Török
Anikó Pósa https://orcid.org/0000-0003-2167-2888
Csaba Varga
Krisztina Kupai https://orcid.org/0000-0002-0644-1718

DOI:

https://doi.org/10.14232/abs.2018.2.180-189

Keywords:

dipeptidyl peptidase-4, DPP-4 inhibitors, hyperlipidemia, infarct size, ischemia-reperfusion injury, NOS, TRP channels

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.

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