Effect of DPP-4 inhibitor sitagliptin against ischemia-reperfusion (I/R) injury in hyperlipidemic animals
| Autor: | Anikó Pósa, Amin Al-awar, Krisztina Kupai, Renáta Szabó, Gergő Szűcs, Nikoletta Almási, Szilvia Török, Csaba Varga, Rudolf Ménesi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
chemistry.chemical_classification
business.industry medicine.medical_treatment Ischemia 030204 cardiovascular system & hematology Pharmacology medicine.disease Effective dose (pharmacology) General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Enzyme chemistry Sitagliptin Hyperlipidemia medicine Myocardial infarction General Agricultural and Biological Sciences business Saline 030217 neurology & neurosurgery Dipeptidyl peptidase-4 medicine.drug |
| Zdroj: | Acta Biologica Szegediensis. 62:180-189 |
| ISSN: | 1588-4082 1588-385X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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