Impact of Finasteride Administration on Neuroactive Steroid Levels To Induce Persistent Sexual Side Effects and Anxious/Depressive Disorders and the Possible Protective Effect of Vitamin E
Journal Title: International Research Journal of Applied and Basic Sciences - Year 2017, Vol 11, Issue 2
Abstract
Background: With aging, abnormal benign growth of the prostate results in benign prostate hyperplasia (BPH) with concomitant lower urinary tract symptoms. Because the prostate is an androgen target tissue, and transforms testosterone into 5α-dihydrotestosterone (5α-DHT), a potent androgen, via 5α-reductase (5α-R) activity, inhibiting this key metabolic reaction was identified as a target for drug development to treat symptoms of BPH. Nowadays, Finasteride is a relatively frequently prescribed drug in the therapeutic management of BPH and male androgenic alopecia. Conflicting reports have led to two diverse and contradictory recommendations from the use of Finasteride. Histopathologic assessment of the testis is a vital component of drug safety evaluation. The reported adverse effects are notable in some patients, consisting in signs and symptoms that are encountered both during Finasteride administration and after treatment cessation. It is well known that brain and plasma levels of the neurosteroid allopregnanolone (ALLO) increase after acute environmental stress, fact that has been considered a homeostatic mechanism in restoring normal function following stress. Thus, it is of great interest to study the contribution of stress-altered plasma ALLO levels and administration of Finasteride (an ALLO synthesis inhibitor). Clinical data show that cognition and sexuality are two distinct but interrelated environmental functions, most probable due to lateralization process of the brain. Aim: This study was carried out to evaluate the changes of neuroactive steroid ALLO Level in Finasteride treated rats and its relation to induce persistent sexual side effects and anxious/depressive symptoms. The possible protective role of vitamin E was also investigated. Materials and Methods: Forty adult male rats divided into four equal groups: group I which served as the control group; group II, Finasteride group which received Finasteride daily at a dose of 5mg/kg/day; group III, Vitamin E group which received only Vitamin E at a dose of 100 mg/kg bodyweight. Group IV, Finasteride and vitamin E group received Finasteride at a dose of 5mg/kg/day alongside with Vitamin E at a dose of 100 mg/kg. Treatments were administered orally by gavage for 28 days. At the end of the experimental period, the markers of oxidative stress were investigated. The animals were submitted to swim stress test for evaluation of depressive like behavior and estimate the plasma ALLO level before and after acute swimming test. Moreover, the histological and the immunohistochemical changes occur in the rat testes were investigated. Results: Administration of Finasteride showed substantial changes in the seminiferous tubules with loss of the normal architecture. The spermatogenic cells were disorganized, degenerated, and separated from the underlying basement membranes. Some areas of interstitium were wide with congested blood vessels and extensive areas of hemorrhage can also be observed. The immunohistochemical study showed a decrease in the intensity of AR immunostaining in Sertoli, Leydig, and peritubular myoid cells and in the number of PCNA immunopositive germ cells in comparison with control. Co-administration of vitamin E with Finasteride induced improvement in testicular histological changes as well as increase in the number of AR and PCNA immunopositive cells. The immunohistochemical expression of Bax protein was high in the Finasteride group. The Bax expression was low in the control and vitamin E groups. Co-treatment with vitamin E and Finasteride displayed moderate expression on the immunoractivity of Bax. Statistically, There are significantly reduced levels of GSH, SOD and CAT (P˂0.001) with increased in MDA concentration (P˂0.001) in Finasteride treated group compared to control group. While, vitamin E treated group, there is significantly change compared to Finasteride group. As regards the ALLO plasma level, it was found that in Finasteride treated rats (group II); significantly decrease this level when compared with the control. In vitamin E treated rats, there was significant increase when compared with group II. However, there was no significant change in rats taken Finasteride and vitamin E (group IV) when compared with group II. Also, the same result obtained after the animals exposed to stress swim test. The current study demonstrated that vitamin E cannot completely ameliorate the adverse effects of Finasteride but it diminished to some extent the deteriorating changes observed in testicular tissues. Conclusion: Finasteride induced harmful effects in the testicular tissues and CNS. Concomitant administration of vitamin E caused partial improvements.
Authors and Affiliations
Sahar Youssef, Sahar Badr El- Din Mohamed
Keywords
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