Clofibrate PPARα activation reduces oxidative stress and improves ultrastructure and ventricular hemodynamics in no-flow myocardial ischemia.
Peroxisome proliferator-activated receptors (PPAR) play a critical physiological role in energy homeostasis, in inflammation, and a protective role in cardiovascular function. We assessed the antioxidant effect of clofibrate-induced Peroxisome proliferator-activated receptor alpha (PPARα) stimulation on ischemic myocardium on myocardial morphology and hemodynamics. Male Wistar rats (300 g) were distributed into the following groups: (1) Sham, (2) myocardial ischemia vehicle treated (MI-V), and (3) myocardial ischemia clofibrate [100 mg/kg/ intraperitoneally) treated (MI-C). Reactive oxygen species (ROS) and lipid peroxidation increased in MI-V, whereas clofibrate prevented this effect. Superoxide dismutase (SOD)-1 and SOD-2 expression increased 4 times upon PPARα stimulation. SOD-1, SOD-2, and catalase activity also increased in response to clofibrate. eNOS mRNA and tetrahydrobiopterin increased in the MI-C group. Clofibrate was able to decrease Angiotensin II (AngII), AngII AT1-receptor, whereas Ang-(1-7) and AngII AT2-receptor expression increased. Assessment of myocardial morphology and cardiac function show that clofibrate improved histological features and hemodynamic parameters. Our results suggest that PPARα stimulation by clofibrate increases the antioxidant defense, leading to improved cardiac function.
Department of Pharmacology, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico.
Luz
L
Ibarra-Lara
Enrique
E
Hong
Elizabeth
E
Soria-Castro
Juan Carlos
JC
Torres-Narváez
Francisca
F
Pérez-Severiano
Leonardo
L
Del Valle-Mondragón
Luz Graciela
LG
Cervantes-Pérez
Margarita
M
Ramírez-Ortega
Gustavo S
GS
Pastelín-Hernández
Alicia
A
Sánchez-Mendoza
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002994:Clofibrate / Q000494:pharmacology*; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D047493:PPAR alpha / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
D000975:Antioxidants; D002374:Catalase; D002994:Clofibrate; D047493:PPAR alpha; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606292:Sod1 protein, rat