Activation of peroxisome proliferator-activated receptor-α by fenofibrate prevents myocardial dysfunction during endotoxemia in rats*

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To investigate the effects of fenofibrate, an activator of peroxisome proliferator-activated receptor-α, on cardiac function in a rat endotoxemia model.


Prospective, randomized, controlled study.


University research laboratory.


Three-month-old male Wistar rats.


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-α, 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 (NOx 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-α was attenuated, whereas myocardial NOx 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.


Fenofibrate, an activator of peroxisome proliferator-activated receptor-α, 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-α, but not for myocardial NO production or oxidative stress.

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