ABSTRACT
The aim of this study was to evaluate the effect of sildenafil and prostaglandin E1 (PGE1) (drugs used in erectile dysfunction) on production of free radicals in prostate and brain of rat. A single dose of sildenafil (10 mg kg(-1) ) and PGE1 (20 µg kg(-1) ) was given to Sprague-Dawley rats (300 g weight) intraperitoneally. The levels of testosterone were measured in blood. Their brains and prostate glands were separated to measure lipid peroxidation, Na(+) and K(+) ATPase activity, reduced glutathione (GSH) and serotonin levels, by means of validated methods. The levels of testosterone increased slightly in animals treated with sildenafil and PGE1. The activity of total ATPase was increased in the prostate of animals treated with sildenafil + PGE1 but decreased in those that received sildenafil alone. PGE1 caused significant diminution of GSH levels in both organs. Sildenafil increased the levels of serotonine in brain, whereas in prostate they decreased instead. Our results suggest that sildenafil induced changes in GSH levels as well as in the serotonergic metabolism, alone or with PGE1 in prostate and brain, respectively. Thus, the combination therapy may be ideal to sustain the biochemical balance due to biphasic stimulation on brain and prostate.
Subject(s)
Alprostadil/pharmacology , Brain/drug effects , Oxidative Stress/drug effects , Prostate/drug effects , Serotonin/metabolism , Animals , Brain/metabolism , Lipid Peroxidation/drug effects , Male , Piperazines , Prostate/metabolism , Purines , Rats , Rats, Sprague-Dawley , Sildenafil Citrate , Sodium-Potassium-Exchanging ATPase/metabolism , Sulfones , Testosterone/bloodABSTRACT
Some drugs that are clinically used in weight control, like sibutramine, act on the serotonergic metabolism, but its relation with free radical (FR) production in the CNS is still unknown. The aim of the work was to evaluate the effect of sibutramine on FR production. Female and male Wistar rats (250 g weight) were used; the animals received sibutramine (10 mg/kg each 36 hours) intraperitoneally during 15 days. At the end of the study, the rats were sacrificed and their brains used to measure lipid peroxidation (TBARS), Na+, K+ ATPase activity, reduced glutathione (GSH), and tryptophan (TRP) levels, by means of validated methods. The activity of Na+, K+ATPase and total ATPase was increased in males and decreased in females. GSH concentration was increased and the levels of TBARS decreased by an effect related to sibutramine in the female group. Sibutramine decreased TRP concentration in the female group, but increased it in the male one, with respect to the control group. Our results suggest that sibutramine produce an antioxidant effect stimulated by the endogenously produced tryptophan and it protects the fluidity of plasma membrane in rat brain.
