Protective effect of fenofibrate against ischemia‐/reperfusion‐induced cardiac arrhythmias in isolated rat hearts

Abstract

Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-α activator that lowers triglycerides and influences cytochrome P-450 (CYP-450) epoxygenase-dependent arachidonic acid (AA) metabolism. CYP-450 epoxygenase metabolizes AA to epoxyeicosatrienoic acids (EETs). EETs have coronary dilating and cardiac and renal protective properties. Fibrates possess similar properties due to their CYP-450 epoxygenase-inducing properties that lead to increase in endogenous EET production. In the current investigations, fenofibrate (100 mg/kg, orally) for 2 weeks decreased ischemia-/reperfusion (I/R)-induced premature ventricular contractions (PVCs), ventricular tachycardia (VT), and ventricular fibrillation (VF) in the isolated rat hearts. Fenofibrate caused marked inhibition of the reperfusion-induced cardiac arrhythmias. The incidence of reperfusion-induced VF decreased from 80% in the control vehicle-treated animals to 33% in the fenofibrate-treated animals (P < 0.001). PVCs were also significantly (P < 0.01) decreased from 223.2 ± 51 in control vehicle-treated animals to 136.8 ± 22 in fenofibrate-treated animals. Total duration of reperfusion-induced VT decreased from 29.2 ± 6.3 s in control, vehicle-treated animals to 4.8 ± 1.3 s in fenofibrate-treated animals, P < 0.001. Heart rate and perfusion pressure were not significantly affected by fenofibrate pretreatment. Diltiazem, a clinically used anti-arrhythmic agent, produced complete protection against I/R-induced cardiac arrhythmias in this model reducing the incidence of VF from 80% in control, vehicle-treated animals to 10% in diltiazem-treated hearts. These findings indicate that fenofibrate suppresses arrhythmias in isolated rat hearts subjected to I/R-induced injury.

Role of PPAR‐α agonist fenofibrate in the treatment of induced benign prostatic hyperplasia with dysplastic changes in rats

“…However, on co‐administration of FEN to BPH induced group (group V) showed moderate increase in apoptosis explaining the preservation and protection of prostatic tissue. These results are in agreement with previous studies which showed apoptotic effect of FEN in different models .…”

“…These findings are in line with previous studies . On co‐administration of FEN with BPH, there is marked improvement of the measured antioxidant and oxidant parameters indicating the protective effect of FEN against formation of free radicals which is supported by different studies .…”

“…Fenofibrate is not only PPARα agonist but also it has anti‐inflammatory, antiproliferative, apoptotic, and antioxidant effects as approved in different previous studies . These effects explain the protective effect of FEN in the progression of BPH with dysplastic changes.…”

“…As a transcription factor, PPARα can govern multiple biological processes by altering the expression of different target genes . Recently, PPARα stimulation has been involved in controlling pathogenesis of different models of injury and diseases and it showed marvelous protective effect depending on its profound anti‐inflammatory, antioxidant roles, controlling metabolic functions, and regulation of apoptotic process .…”

“…PPARα stimulation increases expression of SOD, glutathione reductase, GPx and glutathione‐S‐transferase gene expression resulting in an increased antioxidant and redox state. Moreover, PPARα activation represses nuclear factor kappa B and the activator protein‐1 signaling pathways so that it could down regulate the inflammatory response and oxidative stress .…”