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PPAR Research
Volume 2016 (2016), Article ID 8237264, 14 pages
http://dx.doi.org/10.1155/2016/8237264
Research Article

Fenofibrate plus Metformin Produces Cardioprotection in a Type 2 Diabetes and Acute Myocardial Infarction Model

1Department of Pharmacobiology, Research and Advanced Studies Center, National Polytechnic Institute (IPN), Calzada de los Tenorios No. 235, Colonia Granjas Coapa, Tlalpan, 14330 Mexico City, Mexico
2Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Colonia Sección XVI, Tlalpan, 14080 Mexico City, Mexico
3Department of Neurochemistry, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Insurgentes Sur No. 3877, Colonia La Fama, Tlalpan, 14269 Mexico City, Mexico

Received 7 January 2016; Accepted 18 February 2016

Academic Editor: Yanbo Fan

Copyright © 2016 Víctor Hugo Oidor-Chan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We investigated whether fenofibrate, metformin, and their combination generate cardioprotection in a rat model of type 2 diabetes (T2D) and acute myocardial infarction (AMI). Streptozotocin-induced diabetic- (DB-) rats received 14 days of either vehicle, fenofibrate, metformin, or their combination and immediately after underwent myocardial ischemia/reperfusion (I/R). Fenofibrate plus metformin generated cardioprotection in a DBI/R model, reported as decreased coronary vascular resistance, compared to DBI/R-Vehicle, smaller infarct size, and increased cardiac work. The subchronic treatment with fenofibrate plus metformin increased, compared with DBI/R-Vehicle, total antioxidant capacity, manganese-dependent superoxide dismutase activity (MnSOD), guanosine triphosphate cyclohydrolase I (GTPCH-I) expression, tetrahydrobiopterin : dihydrobiopterin (BH4 : BH2) ratio, endothelial nitric oxide synthase (eNOS) activity, nitric oxide (NO) bioavailability, and decreased inducible NOS (iNOS) activity. These findings suggest that PPARα activation by fenofibrate + metformin, at low doses, generates cardioprotection in a rat model of T2D and AMI and may represent a novel treatment strategy to limit I/R injury in patients with T2D.