OBJECTIVE: To investigate the effects of fenofibrate, an activator of peroxisome proliferator-activated receptor-alpha, on cardiac function in a rat endotoxemia model. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Three-month-old male Wistar rats. INTERVENTIONS: Animals were fed with standard diet containing no drug or fenofibrate (0.2%) for 14 days. They were then injected intravenously with either 5 mg/kg lipopolysaccharide (LPS and fenofibrate + LPS groups) or saline (control and fenofibrate groups). MEASUREMENTS AND MAIN RESULTS: In the LPS group, body weight loss, metabolic acidosis, and thrombocytopenia confirmed presence of systemic endotoxemia. LPS administration resulted in an early peak in plasma tumor necrosis factor-alpha, decreased cardiac contractility (isolated and perfused heart), reduced myofilament Ca2+ sensitivity (Triton-skinned cardiac fibers), and increased left ventricular nitric oxide (NO) end-oxidation products (NO(x) and NO2), without evidence of myocardial oxidative stress (thiobarbituric acid-reactive substances and antioxidant enzyme activities). Fenofibrate pretreatment (fenofibrate + LPS group) did not alter signs of endotoxemia but prevented reductions in both cardiac contractility and myofilament Ca2+ sensitivity. The peak of plasma tumor necrosis factor-alpha was attenuated, whereas myocardial NO(x) and NO2 remained similar to the LPS group. Oxidative stress was suggested from moderate increase in cardiac thiobarbituric acid-reactive substances and reduced glutathione peroxidase activity. CONCLUSION: Fenofibrate, an activator of peroxisome proliferator-activated receptor-alpha, may prevent endotoxemia-induced cardiac dysfunction and reduction in myofilament Ca2+ sensitivity. Our data also suggest a mediating role for early peak plasma tumor necrosis factor-alpha, but not for myocardial NO production or oxidative stress.
OBJECTIVE: To investigate the effects of fenofibrate, an activator of peroxisome proliferator-activated receptor-alpha, on cardiac function in a ratendotoxemia model. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Three-month-old male Wistar rats. INTERVENTIONS: Animals were fed with standard diet containing no drug or fenofibrate (0.2%) for 14 days. They were then injected intravenously with either 5 mg/kg lipopolysaccharide (LPS and fenofibrate + LPS groups) or saline (control and fenofibrate groups). MEASUREMENTS AND MAIN RESULTS: In the LPS group, body weight loss, metabolic acidosis, and thrombocytopenia confirmed presence of systemic endotoxemia. LPS administration resulted in an early peak in plasma tumor necrosis factor-alpha, decreased cardiac contractility (isolated and perfused heart), reduced myofilament Ca2+ sensitivity (Triton-skinned cardiac fibers), and increased left ventricular nitric oxide (NO) end-oxidation products (NO(x) and NO2), without evidence of myocardial oxidative stress (thiobarbituric acid-reactive substances and antioxidant enzyme activities). Fenofibrate pretreatment (fenofibrate + LPS group) did not alter signs of endotoxemia but prevented reductions in both cardiac contractility and myofilament Ca2+ sensitivity. The peak of plasma tumor necrosis factor-alpha was attenuated, whereas myocardial NO(x) and NO2 remained similar to the LPS group. Oxidative stress was suggested from moderate increase in cardiac thiobarbituric acid-reactive substances and reduced glutathione peroxidase activity. CONCLUSION:Fenofibrate, an activator of peroxisome proliferator-activated receptor-alpha, may prevent endotoxemia-induced cardiac dysfunction and reduction in myofilament Ca2+ sensitivity. Our data also suggest a mediating role for early peak plasma tumor necrosis factor-alpha, but not for myocardial NO production or oxidative stress.
Authors: Ion A Hobai; Emmanuel S Buys; Justin C Morse; Jessica Edgecomb; Eric H Weiss; Antonis A Armoundas; Xiuyun Hou; Alok R Khandelwal; Deborah A Siwik; Peter Brouckaert; Richard A Cohen; Wilson S Colucci Journal: Am J Physiol Heart Circ Physiol Date: 2013-08-09 Impact factor: 4.733
Authors: Carlos R Cámara-Lemarroy; Francisco J Guzman-DE LA Garza; Paula Cordero-Perez; Juan M Ibarra-Hernandez; Linda E Muñoz-Espinosa; Nancy E Fernandez-Garza Journal: Exp Ther Med Date: 2015-01-19 Impact factor: 2.447