Noa PM, Mendoza CS, Valle CM, Mas FR

Language: Spanish
References: 31
Page: 27-34
PDF size: 232.88 Kb.

ABSTRACT

Objective: To evaluate the effect of D-004, Saw Palmetto (SP) and Tamsulosin, on apoptosis, in prostatic hyperplasia induced by testosterone and phenylephrine in rats.
Material and methods: Two experimental series were studied for induction of prostatic hyperplasia (PH). In serie1 PH was induced by testosterone. Rats were distributed in 6 groups: negative and positive controls, 3 groups treated with D004 at doses of 200, 400 and 800 mg/kg, and other of SP (400 mg/kg). In serie 2 phenylephrine was administered. Five groups were studied: negative and positive control, D-004 and SP (400mg/kg) and Tamsulosin (0.4mg/kg). Samples of ventral prostate were processed for immunohistochemical study of apoptosis. The apoptotic index (AI) was analyzed as the primary efficacy variable.
Results: In positive controls of series 1 and 2, a significative reduction of AI was observed vs negative controls. In serie1, samples of treated animals with D-004, and SP showed significative elevation of AI, vs positive control, as in serie 2, D-004 and SP treated groups showed significative elevation of AI vs positive control, as in Tamsulosin group.
Conclusions: D-004 prevented the reduction of induced apoptosis by T and FE in rats, as same of SP, and may possible to relate at first, its effect on HP with apoptosis induction effect. Tamsulosin showed a lesser effect.

REFERENCES

1. Barboza Hernández M. Hiperplasia prostática benigna. Revista médica Sinergia. 2017; 2 (8) : 11-16

2. Lim K B. Epidemiology of clinical benign prostatic hyperplasia. Asian J Urol. 2017; 4(3): 148–151.

3. Foo K T. Pathophysiology of Clinical Benign Prostatic Hyperplasia (BPH). Asian J Urol. 2017; 4(3): 152–157.

4. Braeckman J, and Denis L. Management of BPH then 2000 and now 2016-From BPH to BPO. Asian J Urol. 2017; 4(3): 138–147.

5. Martínez LE, González A, Olzábal JP, Pardo HD. Diagnóstico y tratamiento de la hyperplasia prostática beningna. Rev Progaleno 2018; 1 (2):133-147. Carson C, Rittmaster R. The role of dihydrotestosterone in benign prostatic hyperplasia. Urol. 2003; 61 (Suppl 1): 2-7

6. Kim E, Brokman J, Andriole G. The use of 5 alpha reductase inhibitors in the treatment of benign prostatic hyperplasia. Asian J Urol 2018; 5(1):28-32 Sandhu JS, Te AE. The role of 5 alpha-reductase inhibition as monotherapy in view of the MTOPS data. Curr. Urol. Rep. 2004; 5: 274-279

7. Domínguez-Domínguez C, Calderón-Ospina C. Postural hypotension associated with inappropiate choice of drug treatment of benign prostatic hyperplasia. Rev Colomb cienc quim farm. 2015; 44 (3): Roehrborn CG, Schwinn DA. Alpha-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. J. Urol. 2004; 171:1029-1035.

8. Kwon Y. Use of Saw Palmetto (Serenoa repens) extract for benign prostatic hyperplasia. Food Sci Biotecnol. 2019; 28 (6):1599- 1606. Gerber GS. Saw palmetto for the treatment of men with lower urinary tract symptoms. J Urol 2000; 163:1408-1414.

9. Laguna A, Rodríguez E, González V, et al, inventors, Laboratorios Dalmer SA, assignee. Pharmaceutical composition and procedure for the prevention and treatment of prostate hyperplasia and prostatitis obtained from the fruit of Roystonea regia (Cuban royal palm) Cuba patent PCT/CU/2004/00004

10. Arruzazabala ML, Carbajal D, Mas R, Molina V, Rodríguez E, González V. Preventive effects of D-004, a lipid extract from Cuban royal palm (Roystonea regia) fruits, on testosterone-induced prostate hyperplasia in intact and castrated rodents. Drugs Exp Clin Res. 2004; 30 (5-6): 227-33.

11. Arruzazabala ML, Molina V, Carbajal D, Mas R, González V, Rodríguez E and Marrero D. Composition changes of lipid extracts of Roystonea regia fruits of different ripening stages influence their effects on testosterone-induced prostate enlargement in rats. Latin Am J Pharm. 2008; 27: 41-45

12. Arruzazabala ML, Carbajal D, Mas R, Molina V and González V, Rodríguez E. Preventive effects of D-004, a lipid extract from Cuban royal palm (Rostoynea regia) fruits, on prostate hyperplasia induced with testosterone on intact and castrated rodents. Drugs Exptl Clin Res. 2004; XXX: 227- 234.

13. Carbajal D, Arruzazabala ML, Mas R, Molina V, Rodríguez E, González V. Effect of D-004, a lipid extract from Cuban Royal Palm fruit, on inhibiting prostatic hypertrophy induced with testosterone or dihydrotestosterone in a rat model: A randomized controlled study. Curr Ther. Res. 2004; 65: 505 – 514.

14. Noa, M, Arruzazabala, ML, Carbajal, D, Mas R and Molina V. Effect of D-004, a lipid extract from Cuban royal palm fruit, on histological changes of prostate hyperplasia induced with testosterone in rats. Int J Tiss React. 2005; 27: 193-198.

15. Arruzazabala ML, Mas R, Molina V, Noa M and Carbajal D. Effect of D-004, a lipid extract from the fruits of Cuban royal palm, on the atypical prostate hyperplasia induced with phenylephrine in rats. Drug R&D. 2006; 7: 233- 224.

16. Arruzazabala ML, Molina V, Mas R and Carbajal D. Effects of D-004, tamsulosin and the combined therapy D004 plus tamsulosin on urodynamic changes induced with phenylephrine in rats. Arzneimittel-Forschung Drug Res.2008; 58: 81-85.

17. Carbajal D, Molina V, Mas R and Arruzazabala M.L. Therapeutic effect of D-004 a lipid extract from Roystonea regia fruits on prostate hyperplasia induced in rats. Drugs Exp Clin Res. 2005; 31:193-197.

18. Molina V, Arruzazabala ML, Carbajal D and Mas R. Effects of D-004 plus finasteride on prostate hyperplasia induced with testosterone in rats. Latin Am J of Pharm. 2007; 26: 536-540.

19. Minutoli R, Rinaldi M, Marini H, Irrera N, Crea G, Lorenzini C. Apoptotic pathways linked to endocrine system as potential therapeutic targets ffor benign prostatic hyperplasia. Int J Molec Sci. 2016; 17 (8):1311-1317. Tahmatzopoulos A, Kyprianou N. Apoptotic impact of alpha1-blockers on prostate cancer growth: a myth or an inviting reality? Prostate. 2004; 1: 91-100.

20. M Demir, Akin Y, Gulut M, Buyukfirat E, Ciftei H, Yeni E. Evaluation of apoptosis indexes in currently used oral alpha blockers in prostate: a pilot study. Int Braz J Urol. 2018; 44 (3) http://doi.org/10.1590/s1677-5538 ibju.2017.0668 Duman I, Arisan S, Büyüktunçer D, Çaflkurlu T, Sönmez C, Palavan Ünsal N Apoptosis detection by TUNEL assay in BPH patients J of Cell and Molec Biol. 2004; 3: 103-107.

21. Yuan Y, Yang J, Zhu W, Liu T, He J, Zhou Q, et al. Qianlongtong Inhibits Proliferation and Induces Apoptosis of Hyperplastic prostate cells. Am J Men’s Health 2018; 12(5): 1548-1553

22. Opoku-Acheampong A, Henningson JN, Lindshield B. The impact of finasteride and dutasteride treatments on proliferation,apoptosis, 5 alpha reductase 1 and 5 alpha reductase 2 in TRAMP mouse prostate. Heliyon 2017; 3 (7): e 00360 doi:10.1016/j.heliyon.2017.e 00360 Sutton, M T, Yingling, M, Vyas A, Atiemo H, Borkowski A, Jacobs, S C. Finasteride targets prostate vascularity by inducing apoptosis and inhibiting cell adhesion of benign and malignant prostate cells. The Prostate. 2006; 66: 1194–1202.

23. López-Ramos H, Moreno M, Patiño G, Rasch-Isla A, Dallos A, Fernández N. Guía de manejo de la hiperplasia prostática benigna. Sociedad colombiana de urología. Guía de práctica clínica 2015; 24 (3): 187.e1-187.e32 doi:10.1016/j.uroco.2015.04.005 Kyprianou N, Jacobs SC. Induction of apoptosis in the prostate by alpha1-adrenoceptor antagonists: a novel effect of “old” drugs. Curr Urol Rep. 2000; 1(2):89-96.

24. Bayne CW, Ross M, Donnelly F, Habib FK. The selectivity and specificity of the actions of the lipido-sterolic extract of Serenoa repens (Permixon) on the prostate. J Urol 2000; 164: 876–81.

25. Vacherot F, Azzouz M, Gil-Diez-De-Medina S, Colombel M, De La Taille A, Lefrere Belda MA, et al. Induction of apoptosis and inhibition of cell proliferation by the lipido-sterolic extract of Serenoa repens (LS ESr, Permixon®) in benign prostatic hyperplasia. Prostate. 2000; 45: 259–66.

26. Hill B, Kyprianou N. Effect of permixon on human prostate cell growth: lack of apoptotic action. Prostate. 2004; 61(1):73-80.

27. Minutoli L, Altavilla D, Marini H, Rinaldi M, Irrera N, Pizzino G et al. Inhibitors of apoptosis proteins in experimental benign prostatic hyperplasia: effects of serenoa repens, selenium and lycopene. J Biomed Science. 2014; 21: 19-26.

28. Benning C, Kyprianou N. Quinazoline-derived 1-adrenoceptor antagonists induce prostate cancer cell apoptosis via an 1-adrenoceptor-independent action. Cancer Res 2002 Jan 15; 62(2): 597-602.

29. Anglin IE, Glassman DT, Kyprianou N. Induction of prostate apoptosis by α1-adrenoceptor antagonists: mechanistic significance of the quinazoline component. Prostate Cancer and Prostatic Dis. 2002; 5: 88-95

30. Batty M, Pugh R, Rathinam I, Simmonds J, Walker E, Forbes A. The role of alfa 1 adrenoceptor antagonists in the treatmen of prostate and others cancers. Int J Mol Sci. 2016; 17 (8): 1339-1364. Kyprianou N. Doxazosin and Terazosin Suppress Prostate Growth by Inducing Apoptosis: Clinical Significance. The J Urol 2003; 169(4): 1520-1525.

31. Elberry A, Mufti Sh, Al-Maghrabi J, Abdel-Sattar E, Ashour O, Ghareib S, Mosli H. Anti-inflammatory and antiproliferative activities of date palm pollen (Phoenix dactylifera) on experimentally-induced atypical prostatic hyperplasia in rats. J Inflam 2011; 8: 40-45.