Erectile dysfunction medication induced-changes in plasma levels of homocysteine and antioxidant enzyme activities as risk factors for cardiovascular disease

摘要

ObjectiveDrugs for erectile dysfunction (ED) act by vasodilatation. Hyperhomocysteinaemia is an independent risk factor for premature atherosclerosis, venous thrombosis and other cardiovascular diseases in both men and women. In addition, oxidative stress has long been regarded as a key pathophysiological mediator that eventually leads to cardiovascular disease, whereas oxidative stress is alleviated by antioxidant enzymes such as superoxide dismutase (SOD) and catalase. The aim of the present study was to determine the levels of plasma homocysteine and antioxidant enzymes in male rats given ED drugs.MethodsMale rats were given a daily dose of 1.48mg/kg body weight sildenafil citrate (Viagra?), 0.285mg/kg vardenafil (Levitra?) or 0.285mg/kg tadalafil (Cialis?) for 3weeks, and plasma levels of homocysteine, SOD and catalase were measured; high- and low-density lipoproteins, total cholesterol and triglycerides were also determined.ResultsThe level of homocysteine was increased by 93% and 67% in plasma of sildenafil- and vardenafil-treated rats, respectively, whereas tadalafil did not change the level significantly. Sildenafil and vardenafil also increased SOD activity by 35% and 46%, respectively; and sildenafil, vardenafil and tadalafil increased the activity of catalase by 33%, 50% and 43%, respectively. A nonsignificant increase in the level of total cholesterol was seen after treatment with all the drugs, and sildenafil, vardenafil and tadalafil increased the levels of high-density lipids by 25%, 41%, and 25%, respectively.ConclusionThe ED medications sildenafil and vardenafil increase the levels of homocysteine and antioxidant enzyme activities. Tadalafil appeared to be safer than the other two drugs, as it did not change the level of homocysteine. Patients taking sildenafil or vardenafil should therefore be advised to take vitamin B12and folic acid in order to reduce the level of homocysteine, as these vitamins play an important role in biotransformation of homocysteine into methionine.