Effect of flutamide and two novel synthetic steroids on GABA, glutamine and some oxidative stress markers in rat brain and prostate.

Flutamide is a steroid used to treat androgen-dependent disorders and as antiepileptic, but it induces a number of non-desirable side effects. This work was aimed at assaying the effect of flutamide and two novel synthetic steroids on the levels of GABA, glutamine and oxidative stress markers. Male Wistar rats (weight 180 g) received a single diazepam dose (5 mg/kg) 30 min prior to sacrifice (group A). Group B, flutamide; group C, 16ß-methyl-17α-benzoyloxypregnen-4-en-3,20-dione; group D, estrone-3-hemisuccinate; group E, testosterone; group F, progesterone; all administered intraperitoneally at 10 mg/kg, daily for 3 days. Brain and prostate were obtained to assess lipid peroxidation (TBARS), Na(+) , K(+) ATPase activity, reduced glutathione (GSH), γ-amino butiric acid (GABA), glutamine and serotonin (5-HT) concentrations through spectrophotometry, fluorescence and HPLC. GABA levels increased and glutamine decreased in group A (P < 0.05). Total ATPase activity increased in group F and TBARS decreased in group B (P < 0.05). GSH decreased in A, B and C groups. 5-HT increased in group A and the prostate weight was increased in group E. The conclusion is that 16ß-methyl-17α-benzoyloxypregnen-4-en-3,20-dione may be considered novel and promising to treat androgen-dependent diseases and epilepsy, since it showed an antioxidant effect and seemed to impair the GABAergic and serotonergic metabolism.

Effect of orlistat on lipid peroxidation, Na+, K+ ATPase, glutathione and serotonin in rat brain.

The aim of this study was to evaluate the effect of orlistat, a drug used in weight loss, on 5-HT and indicators of oxidative stress in rat brain. Orlistat, 12 mg/kg was administered to Wistar rats as single dose or successive doses on 3 consecutive days. Blood glucose and oxidative stress indicators were detected by measurement of lipid peroxidation, Na+, K+ ATPase, glutathione and serotonin levels using previous validated methods. The levels of glucose decreased in rats receiving successive doses. The activity of Na+, K+ ATPase and total ATPase was reduced in rats receiving successive doses, while the level of lipid peroxidation increased slightly in both groups. Glutathione underwent significant reduction in the successive doses group (p < 0.05). 5-HT increased significantly after single dose treatment (p < 0.05). Orlistat can induce pro-oxidant effects in the brain due to alteration of serotonergic metabolism and the reduction of glutathione.