Summary and Conclusion
MI is caused by an imbalance between myocardial blood demand and the coronary blood delivery that leads death of myocardium and then mechanical, electrical, structural, and biochemical changes of the cardiac muscle (El-Gohary and Allam, 2017). Acute MI is a leading cause of morbidity and mortality of CVD in developed as well as in developing countries (Kendir et al.,2018). In Egypt, the prevalence of IHD is 8.3% (Zaki et al., 2018). The development of MI involves oxidative stress (Taleb et al., 2018) that stems from an imbalance between oxidative radicals and anti oxidative enzymes (Chandra et al., 2015). TGFβ, a multifunctional cytokine, (Massagué , 2012) appeared to play a vital role in this process. It promotes the secretion of numerous proteins of the extracellular matrix including collagens, fibronectin and proteoglycans causing MI if not treated properly it would lead to development of cardiac fibrosis and scar formation (Spender et al., 2013). Additionally, it promotes myocyte apoptosis, reduction of myocyte proliferation thus, increases infarction size (Euler, 2015). So, searching for protective agents becomes an urgent need.
The PDE5i ,Sil, is a widely used medication for treatment of erectile dysfunction and pulmonary arterial hypertension (Wang et al.,2014). It also, decreases platelet aggregation and the risk of obesity complications (Johann et al., 2018). However, its prophylactic role against MI still a matter of debate and controversy. So, we aimed to illustrate this issue.
Vit. E is a fat-soluble, it is incorporated into cell membranes, which are therefore protected from oxidative damage. It’s is the most abundant and important lipophilic radical-scavenging antioxidant in vivo (Niki,2014). It acts as the first line of defense against lipid peroxidation, protecting the cell membranes from free radical attack (Rizvi et al.,2014). It is characterized by being safe, effective, easy obtained, cheap and a vital vitamin for good health (Ross et al., 2014). So, we aimed to declare its prophylactic impact on MI.
Subsequently, this study was designed to investigate the potential protective effect of Sil and Vit. E on ISO-induced MI targeting the redox status and TGFβ as a suggested mechanisms.
This study was carried out on 30 adult Wistar albino male rats divided into 5 equal groups as follow: Control group, MI group in which MI was induced by using single dose of ISO at a dose 75mg/kg injected intraperitoneally, Sil+MI this group received oral Sil at a dose of 10 mg/kg/day for 3 weeks before induction of myocardial injury by ISO, Vit. E+MI this group received oral Vit. E at a dose of 100 IU/kg/day for 3 weeks before induction of myocardial injury by ISO, Sil+Vit. E+MI this group received both sildenafil and Vit. E oral administration then MI was induced.
Parameters chosen to assess the protective effect of Sil and Vit. E on ISO-induced MI included ECG waves (Q , R , T ) , heart rate, serum CK-MB, cardiac SOD , cardiac MDA , cardiac histopathological injury score and TGFβ expression score. The obtained results of this study could be summarized as follow: Induction of MI by ISO resulted in significant changes in ECG waves (Q , R , T ); deep Q , short R and inverted T; also, significant increases in heart rate, serum CK-MB and cardiac MDA, cardiac histopathological injury score and TGFβ expression score with significant decreases in cardiac SOD when compared with the control group. Moreover, interventions with Sil or Vit. E significantly reversed the aforementioned parameters with better impact of their combination.
From the above results we concluded that Sil or Vit. E can exert a protective effect against ISO induced MI with more beneficial effect of their combination approach with targeting the redox balance restoration and TGFβ inhibition. Denoting that their prophylactic impact could be exerted on either prevention of MI occurrence or reducing risk of its complication by scar formation and fibrosis.
|
