Sildenafil inhibits the ROS production by xanthine oxidase

Xanthine oxidase (XO) catalyzes the hydroxylation of a wide variety of substrates, including purines, pirimidines, pterins d aldehydes, to acids1. At relatively high oxygen pressure, it generates reactive oxygen species (ROS) as superoxides and hydroxyl radicals. The XO, detected in endothelial and epithelial cell outer surface, has been involved in ischemia/reperfusion injury1,2. Furthermore, XO-ROS production has been implicated in chronic hearth failure, inflammatory diseases, LDL oxidation, atherosclerosis, hypertension, cancer, aging1. Allopurinol, a hypoxanthine analogue developed as xanthine oxidase inhibitor 30 years ago, and oxypurinol, its oxidation product, have proved to be effective in the treatment of these conditions both in experimental animals and human clinical trials1. Recent studies have shown the significant benefits of sildenafil, an inhibitor of type 5 phosphodiesterase, in patients with pulmonary hypertension, and an endothelium enhancing effect in preconditioning prior to ischemia/reperfusion3,4. As allopurinol/oxypurinol and sildenafil exhibit a marked structural analogy, we assayed the effect of this drug on the purified enzyme and in human prostatic cell cultures. The 80-100% inhibition of the ROS production by the enzyme bound to the external membrane of prostatic cells suggests that this mechanism may be of primary importance for the protective effects of the drug on epithelial cell