Fenofibrate plus Metformin Produces Cardioprotection in a Type 2 Diabetes and Acute Myocardial Infarction Model
Víctor Hugo Oidor-Chan,
Enrique Hong,
Francisca Pérez-Severiano,
Sergio Montes,
Juan Carlos Torres-Narváez,
Leonardo del Valle-Mondragón,
Gustavo Pastelín-Hernández,
Alicia Sánchez-Mendoza
Affiliations
Víctor Hugo Oidor-Chan
Department 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
Enrique Hong
Department 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
Francisca Pérez-Severiano
Department of Neurochemistry, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Insurgentes Sur No. 3877, Colonia La Fama, Tlalpan, 14269 Mexico City, Mexico
Sergio Montes
Department of Neurochemistry, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Insurgentes Sur No. 3877, Colonia La Fama, Tlalpan, 14269 Mexico City, Mexico
Juan Carlos Torres-Narváez
Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Colonia Sección XVI, Tlalpan, 14080 Mexico City, Mexico
Leonardo del Valle-Mondragón
Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Colonia Sección XVI, Tlalpan, 14080 Mexico City, Mexico
Gustavo Pastelín-Hernández
Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Colonia Sección XVI, Tlalpan, 14080 Mexico City, Mexico
Alicia Sánchez-Mendoza
Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Colonia Sección XVI, Tlalpan, 14080 Mexico City, Mexico
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.
