The potential cardioprotective effects of Febuxostat versus Cilostazol on Isoproterenol induced cardiac dysfunction in rats

Myocardial infarction causes an acute condition of necrosis of the myocardium resulting in increased production of free radicals and decreased levels of antioxidants. It was proposed that Febuxostat reduced myocardial oxidative stress and suppressed apoptosis. Cilostazol used to treat claudication has a growing evidence, suggesting that Cilostazol could be cardioprotective. This work aims to highlight the potential protective effect of pretreatment with Febuxostat vs. Cilostazol on Isoproterenol induced cardiac toxicity in rats. Thirty-six male albino rats were divided into 6 groups (6 rats each); control, Febuxostat, Cilostazol, Isoproterenol, Febuxostat+Isoproterenol and Cilostazol+Isoproterenol groups. Cardiotoxicity was induced by subcutaneous injection of Isoproterenol 100 mg kg on the 13th and14th day of the experiment. ECG parameters were assayed. Measurement of cardiac TNF-α level, serum troponin and histopathological changes were also performed. Pretreatment with Febuxostat led to significant increase in heart rate and a significant decrease in QT and QTC intervals compared to Cilostazol. Cilostazol led to significant reduction in TNF-α and insignificant reduction of cardiac troponin levels compared to Febuxostat. Isoproterenol led to arrhythmia in 33% of rats, Febuxostat led to arrhythmia in 50% of rats, while Cilostazol did not lead to any arrhythmias. Pretreatment with Febuxostat and Cilostazol led to significant improvement in the pathological changes caused by Isoproterenol; however, there was no statistically significant difference between them. Pretreatment with Cilostazol is more cardioprotective than Febuxostat as it led to more reduction in TNF-α without increasing arrhythmias or affecting QT and QTC intervals as compared to Febuxostat. Key words:  Cardioprotective, cilostazol, febuxostat, isopreterenol, cardiac dysfunction.