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Molecules 2017, 22(1), 31; doi:10.3390/molecules22010031

Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II

1
Department of Pharmacology, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
2
Department of Pathology, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
3
Department of Molecular Biology, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
4
Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y de la Nutrición “Salvador Zubirán”, Vasco de Quiroga 15, Sección XVI, Tlalpan, México City 14000, Mexico
5
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, México City 04510, Mexico
6
Department of Physiology, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Sección XVI, Tlalpan, México City 14080, Mexico
L.I.-L. and M.S.-A. share the first authorship of this paper.
*
Author to whom correspondence should be addressed.
Academic Editors: Luciano Saso, László Dux, Grzegorz Wegrzyn and Tamás Csont
Received: 24 October 2016 / Revised: 4 December 2016 / Accepted: 20 December 2016 / Published: 28 December 2016
(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)
View Full-Text   |   Download PDF [5084 KB, uploaded 28 December 2016]   |  

Abstract

Renin-angiotensin system (RAS) activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS) and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II)/Angiotensin II type 1 receptor (AT1) and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia. Control and MetS rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); and (c) fenofibrate-treated myocardial infarction (MI-F). Treatment with fenofibrate significantly reduced triglycerides, non-high density lipoprotein cholesterol (non-HDL-C), insulin levels and insulin resistance index (HOMA-IR) in MetS animals. MetS and MI increased Ang II concentration and AT1 expression, favored myocardial oxidative stress (high levels of malondialdehyde, overexpression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), decreased total antioxidant capacity and diminished expression of superoxide dismutase (SOD)1, SOD2 and catalase) and inhibited expression of the insulin signaling cascade: phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PkB, also known as Akt)/Glut-4/endothelial nitric oxide synthase (eNOS). In conclusion, fenofibrate treatment favors an antioxidant environment as a consequence of a reduction of the Ang II/AT1/NOX4 signaling pathway, reestablishing the cardiac insulin signaling pathway. This might optimize cardiac metabolism and improve the vasodilator function during myocardial ischemia. View Full-Text
Keywords: metabolic syndrome; insulin resistance; myocardial ischemia; fenofibrate; oxidative stress; angiotensin II metabolic syndrome; insulin resistance; myocardial ischemia; fenofibrate; oxidative stress; angiotensin II
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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. (CC BY 4.0).

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Ibarra-Lara, L.; Sánchez-Aguilar, M.; Sánchez-Mendoza, A.; Del Valle-Mondragón, L.; Soria-Castro, E.; Carreón-Torres, E.; Díaz-Díaz, E.; Vázquez-Meza, H.; Guarner-Lans, V.; Rubio-Ruiz, M.E. Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II. Molecules 2017, 22, 31.

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