L-cysteine/hydrogen sulfide pathway: pharmacological approaches in urinary bladder and cardiovascular diseases

Reactive oxygen species (ROS) represent a major cause of myocardial injury and cellular damage during ischemia/reperfusion. Increasing the activity of cellular antioxidant enzymes, cardiomyocytes can protect myocardium tissue against ischemia/reperfusion injury. H2S is produced in mammalian tissue by three different enzymes: cystathionine ?-lyase (CSE), cystationine ?-synthase (CBS) and 3-mercaptopopyruvate sulfurtransferase (3-MST) It has been demonstrated that acute injection of H2S, either prior to ischemia or at reperfusion, markedly ameliorates in vivo myocardial ischemia/reperfusion (MI/R) injury and induces cardioprotection by enhancing eNOS activity, thus increasing myocardial NO bioavailability. Furthermore, H2S exerts antioxidant properties in myocardium through nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signalling. Angiotensin converting enzyme inhibitors (ACEIs) are recommended for the management of myocardial ischemia. Even though ACEIs have been shown to reduce cardiovascular morbidity and mortality in patients affected with myocardial infarction, their cardioprotection is not dependent entirely on inhibition of angiotensin II production. Zofenopril is a sulphydryl-ACEI characterized by high lipophilicity, long-lasting tissue penetration, selective cardiac ACE inhibition and antioxidant and cardioprotective activities. Recently, it has been reported that zofenopril promotes H2S signalling through the upregulation of CSE or by acting as an H2S donor. T