title: Fenofibrate plus Metformin Produces Cardioprotection in a Type 2 Diabetes and Acute Myocardial Infarction Model.
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.
authors.affiliation: 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; Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Colonia Sección XVI, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: Víctor Hugo
authors.initials: VH
authors.lastname: Oidor-Chan
authors.affiliation: 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.
authors.forename: Enrique
authors.initials: E
authors.lastname: Hong
authors.affiliation: Department of Neurochemistry, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Insurgentes Sur No. 3877, Colonia La Fama, Tlalpan, 14269 Mexico City, Mexico.
authors.forename: Francisca
authors.initials: F
authors.lastname: Pérez-Severiano
authors.affiliation: Department of Neurochemistry, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Insurgentes Sur No. 3877, Colonia La Fama, Tlalpan, 14269 Mexico City, Mexico.
authors.forename: Sergio
authors.initials: S
authors.lastname: Montes
authors.affiliation: Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Colonia Sección XVI, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Torres-Narváez
authors.affiliation: Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Colonia Sección XVI, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Del Valle-Mondragón
authors.affiliation: Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Colonia Sección XVI, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pastelín-Hernández
authors.affiliation: Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1, Colonia Sección XVI, Tlalpan, 14080 Mexico City, Mexico.
authors.forename: Alicia
authors.initials: A
authors.lastname: Sánchez-Mendoza