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

Abstract

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, 16β-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 16β-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.

Testicular morphometry of rats with Walker 256 tumor supplemented with L-glutamine

“…This reduction may be associated with an interference in testicular androgenic capacity, since it was shown that patients with non-androgenic cancers showed reduction in serum testosterone levels, which was always linked to the individuals' metabolic status and hypogonadism (Fleishman et al, 2010). The L-glutamine supplementation did not increase the number of Leydig cells suggesting that this amino acid was not able to reduce a possible hormonal stress usually found in tumor situations, as observed in studies with testicular cancer and testicular toxicity, as well as hormonal disorders in organs with endocrine activity, such as prostate and others (Calderón Guzmán et al, 2011;Olaniyi et al, 2020;Rotovnik Kozjek et al, 2017)…”