Advertisement

European Journal of Nutrition

, Volume 56, Issue 3, pp 1201–1210 | Cite as

Flaxseed reduces epithelial proliferation but does not affect basal cells in induced benign prostatic hyperplasia in rats

  • Ilma Cely de Amorim Ribeiro
  • Carlos Alberto Soares da Costa
  • Vivian Alves Pereira da Silva
  • Lanna Beatriz Neves Silva Côrrea
  • Gilson Teles Boaventura
  • Mauricio Alves ChagasEmail author
Original Contribution

Abstract

Purpose

This study aimed to quantitatively and qualitatively evaluate the effects of a flaxseed-based diet on the histoarchitecture of the prostate of normal Wistar rats and of rats with induced BPH.

Methods

The study included four experimental groups of ten animals each: casein control group (CCG), who were fed a casein-based diet; flaxseed control group (FCG), who were fed a flaxseed-based diet; hyperplasia-induced casein group (HICG), who were fed a casein-based diet; and hyperplasia-induced flaxseed group (HIFG), who were fed a flaxseed-based diet. Hyperplasia was induced by the subcutaneous implantation of silicone pellets containing testosterone propionate. After 20 weeks, the rats were euthanized and their prostate fixed in buffered formalin. Tissue sections were stained with HE, picrosirius red and immunostained for nuclear antigen p63. Histomorphometric analysis evaluated the epithelial thickness, epithelial area, individual luminal area, and total area of prostatic alveoli.

Results

The mean epithelial thickness obtained for HIFG and HICG was 16.52 ± 1.65 and 20.58 ± 2.86 µm, respectively. The mean epithelial thickness in HICG was greater than that in the other groups tested. HIFG had a smaller epithelial thickness and lower percentage of papillary projections in the prostatic alveoli. No significant difference was observed between CCG and FCG. The total area and mean alveolar area showed no significant differences between the groups. The number of cells immunostained for p63 was not significantly different between the groups evaluated.

Conclusion

These results suggest that flaxseed has a protective effect on the prostate epithelium in BPH-induced animals.

Keywords

Prostate Rats Benign prostatic hyperplasia Diet Flaxseed 

Notes

Acknowledgments

This work was supported by the Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ).

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Nicholson TM, Ricke WA (2011) Androgens and estrogens in benign prostatic hyperplasia: past, present and future. Differentiation 82:184–199CrossRefGoogle Scholar
  2. 2.
    Li SH, Ryu JH, Park SE, Cho YS, Park JW, Lee WJ, Chun YS (2010) Vitamin C supplementation prevents testosterone-induced hyperplasia of rat prostate by down-regulating HIF-1alpha. J Nutr Biochem 21:801–808CrossRefGoogle Scholar
  3. 3.
    Kessler OJ, Keisari Y, Servadio C, Abramovici A (1998) Role of chronic inflammation in the promotion of prostatic hyperplasia in rats. J Urol 159:1049–1053CrossRefGoogle Scholar
  4. 4.
    Demark-Wahnefried W, Price DT, Polascik TJ, Robertson CN, Anderson EE, Paulson DF, Walther PJ, Gannon M, Vollmer RT (2001) Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features. Urology 58:47–52CrossRefGoogle Scholar
  5. 5.
    Demark-Wahnefried W, Robertson CN, Walther PJ, Polascik TJ, Paulson DF, Vollmer RT (2004) Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate specific antigen. Urology 63:900–904CrossRefGoogle Scholar
  6. 6.
    Neven L (2003) Lignans from flax. A solution for men’s health only? Nutraceuticals Now 2003:10–13Google Scholar
  7. 7.
    Verheus M, Gils CHV, Keinan-Boker L, Grace PB, Bingham SA, Peeters PHM (2007) Plasma phytoestrogens and subsequent breast cancer risk. J Clin Oncol 25:648–655CrossRefGoogle Scholar
  8. 8.
    Brzezinsk A, Debi A (1999) Phytoestrogens: The “natural” selective estrogen receptor modulators? Eur J Obstet Gynecol Reprod Biol 85:47–51CrossRefGoogle Scholar
  9. 9.
    Hasler CM, Kundrat S, Wool D (2000) Functional foods and cardiovascular disease. Curr Atherosckler 2:467–475CrossRefGoogle Scholar
  10. 10.
    Kurzer MS, Xu X (1997) Dietary phytoestrogens. Annu Rev Nutr 17:353–381CrossRefGoogle Scholar
  11. 11.
    Thompson LU (1993) Potential health benefits and problems associated with antinutrients in foods. Food Res Int 26:131–149CrossRefGoogle Scholar
  12. 12.
    Evans BA, Griffiths K, Morton MS (1995) Inhibition of 5 alpha-reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids. J Endocrinol 147:295–302CrossRefGoogle Scholar
  13. 13.
    Thompson LU, Robb P, Serraino M, Cheung F (1991) Mammalian lignan production from various foods. Nutr Cancer 16:43–52CrossRefGoogle Scholar
  14. 14.
    Singh KK, Mridula D, Rehal J, Barnwal P (2011) Flaxseed: a potential source of food, feed and fiber. Crit Rev Food Sci Nutr 51:210–222CrossRefGoogle Scholar
  15. 15.
    Lee J, Cho K (2012) Flaxseed sprouts induce apoptosis and inhibit growth in MCF-7 and MDA-MB-231 human breast cancer cells. In Vitro Cell Dev Biol Anim 48:244–250CrossRefGoogle Scholar
  16. 16.
    Velentzis LS, Woodside JV, Cantwell MM, Leathem AJ, Keshtgar MR (2008) Do phytoestrogens reduce the risk of breast cancer and breast cancer recurrence? What clinicians need to know. Eur J Cancer 44:1799–1806CrossRefGoogle Scholar
  17. 17.
    Cardozo LFMF, Chagas MA, Soares LL, Troina AA, Boaventura GT (2010) Exposure to flaxseed during lactation does not alter prostate area or epithelium height but changes lipid profile in rats. Nutr Hosp 25:250–255Google Scholar
  18. 18.
    Miksicek RJ (1994) Interaction of naturally occurring nonsteroidal estrogens with expressed recombinant human estrogen receptor. J Steroid Biochem Mol Biol 49:153–160CrossRefGoogle Scholar
  19. 19.
    Roy-Burman P, Wu H, Powell WC, Hagenkord J, Cohen MB (2004) Genetically defined mouse models that mimic natural aspects of human prostate cancer development. Endocr Relat Cancer 11:225–254CrossRefGoogle Scholar
  20. 20.
    Hayashi N, Sugimura Y, Kawamura J, Donjacour AA, Cunha GR (1991) Morphological and functional heterogeneity in the rat prostatic gland. Biol Reprod 45:308–321CrossRefGoogle Scholar
  21. 21.
    Sarobo C, Lacorte LM, Martins M, Rinaldi JC, Moroz A, Scarano WR, Delella FK, Felisbino SL (2012) Chronic caffeine intake increases androgenic stimuli, epithelial cell proliferation and hyperplasia in rat ventral prostate. Int J Exp Pathol 93:429–437CrossRefGoogle Scholar
  22. 22.
    Kierszenbaum AL, Tres LL (2012) Histology and cell biology: an introduction to pathology. Elsevier, PhiladelphiaGoogle Scholar
  23. 23.
    Kurita T, Medina RT, Mills AA, Cunha GR (2004) Role of p63 and basal cells in the prostate. Development 131:4955–4964CrossRefGoogle Scholar
  24. 24.
    Chagas MA, Babinski MA, Costa WS, Sampaio FJB (2002) Stromal and acinar components of the transition zone in normal and hyperplastic human prostate. BJU Int 89:699–702CrossRefGoogle Scholar
  25. 25.
    Hsu A, Bruno RS, Lohr CV, Taylor AW, Dashwood RH, Bray TM, Ho E (2011) Dietary soy and tea mitigate chronic inflammation and prostate cancer via NFκB pathway in the Noble rat model. J Nutr Biochem 22:502–510CrossRefGoogle Scholar
  26. 26.
    Pour PM, Stepan K (1987) Induction of prostatic carcinomas and lower urinary tract neoplasms by combined treatment of intact and castrated rats with testosterone propionate and N-nitrosobis (2-oxopropyl) amine. Cancer Res 47:5699–5706Google Scholar
  27. 27.
    Scolnik MD, Servadio C, Abramovici A (1994) Comparative study of experimentally induced benign and atypical hyperplasia in the ventral prostate of different rat strains. J Androl 15:287–297Google Scholar
  28. 28.
    Zhang W, Wang X, Liu Y, Tian H, Flickinger B, Empie MW, Sun SZ (2008) Effects of dietary flaxseed lignan extract on symptoms of benign prostatic hyperplasia. J Med Food 11:207–214CrossRefGoogle Scholar
  29. 29.
    Bancroft JD, Cook HC (1994) Manual of histological techniques and their diagnostic application. Churchill Livingstone, EdinburghGoogle Scholar
  30. 30.
    Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diet of laboratory rodents: final report of the American Institute of Nutrition ad hoc Writing Committee on the Reformulation of the AIN-76A rodents diet. J Nutr 123:1939–1951Google Scholar
  31. 31.
    Junqueira LCU, Bignolas GE, Brentani RR (1979) Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections. Histochem J 11:447–455CrossRefGoogle Scholar
  32. 32.
    Arcolino FO, Ribeiro DL, Gobbo MG, Taboga SR, Góes RM (2010) Proliferation and apoptotic rates and increased frequency of p63-positive cells in the prostate acinar epithelium of alloxan-induced diabetic rats. Int J Exp Pathol 91(2):144–154CrossRefGoogle Scholar
  33. 33.
    Jang H, Bae WJ, Yuk SM, Han DS, Ha US, Hwang SY, Yoon SH, Kim SW, Han CH (2014) Seoritae extract reduces prostate weight and suppresses prostate cell proliferation in a rat model of benign prostate hyperplasia. Evid Based Complement Alternat Med 2014:475876. doi: 10.1155/2014/475876 CrossRefGoogle Scholar
  34. 34.
    Carson C, Rittmaster R (2003) The role of dihydrotestosterone in benign prostatic hyperplasia. Urology 61:2–7CrossRefGoogle Scholar
  35. 35.
    Shrivastava A, Gupta VB (2012) Various treatment options for benign prostatic hyperplasia: a current update. J Midlife Health 3:10–19Google Scholar
  36. 36.
    Vargas RA, Oliveira LP, Frankenfeld S, de Souza DB, Costa WS, Favorito LA, Sampaio FJ (2013) The prostate after administration of anabolic androgenic steroids: a morphometrical study in rats. Int Braz J Urol 39:675–682CrossRefGoogle Scholar
  37. 37.
    Bronson FH, Matherne CM (1997) Exposure to anabolic-androgenic steroids shortens life span of male mice. Med Sci Sports Exerc 29:615–619CrossRefGoogle Scholar
  38. 38.
    Bruchovsky N, Lesser B, Van Doorn E, Craven S (1975) Hormonal effects on cell proliferation in rat prostate. Vitam Horm 33:61–102CrossRefGoogle Scholar
  39. 39.
    Clark AS, Harrold EV, Fast AS (1997) Anabolic-androgenic steroid effects on the sexual behavior of intact male rats. Horm Behav 31:35–46CrossRefGoogle Scholar
  40. 40.
    Shahidi NT (2001) A review of the chemistry, biological action, and clinical applications of anabolic-androgenic steroids. Clin Ther 23:1355–1390CrossRefGoogle Scholar
  41. 41.
    Justulin LA Jr, Ureshino RP, Zanoni M, Felisbino SL (2006) Differential proliferative response of the ventral prostate and seminal vesicle to testosterone replacement. Cell Biol Int 30:354–364CrossRefGoogle Scholar
  42. 42.
    Adlercreutz H, Mousavi Y, Clark J, Höckerstedt K, Hämäläinen E, Wähälä K, Mäkelä T, Hase T (1992) Dietary phytoestrogens and cancer: in vitro and in vivo studies. J Steroid Biochem Mol Biol 41:331–337CrossRefGoogle Scholar
  43. 43.
    Hasler CM (1998) Scientific status summary. Functional foods: their role in disease prevention and health promotion. Food Technol 52:63–70Google Scholar
  44. 44.
    Azrad M, Vollmer RT, Madden J, Dewhirst M, Polascik TJ, Snyder DC, Ruffin MT, Moul JW, Brenner DE, Demark-Wahnefried W (2013) Flaxseed-derived enterolactone is inversely associated with tumor cell proliferation in men with localized prostate cancer. J Med Food 16(4):357–360CrossRefGoogle Scholar
  45. 45.
    Said MM, Hassan NS, Schlicht MJ, Bosland MC (2015) Flaxseed suppressed prostatic epithelial proliferation in a rat model of benign prostatic hyperplasia. J Toxicol Environ Health A 78(7):453–465CrossRefGoogle Scholar
  46. 46.
    Hackshaw-McGeagh LE, Perry RE, Leach VA, Qandil S, Jeffreys M, Martin RM, Lane JA (2015) A systematic review of dietary, nutritional, and physical activity interventions for the prevention of prostate cancer progression and mortality. Cancer Causes Control 26(11):1521–1550CrossRefGoogle Scholar
  47. 47.
    Ribeiro ICA, Costa CAS, Pereira VA, Boaventura GT, Chagas MA (2014) Effects of flaxseed flour on the lipid profile of rats submitted to prolonged androgen stimuli. Nutr Hosp 30:825–830Google Scholar
  48. 48.
    Ward WE, Chen J, Thompson LU (2001) Exposure to flaxseed or its purified lignan during suckling only or continuously does not alter reproductive indices in male and female offspring. J Toxicol Environ Health A 64:567–577CrossRefGoogle Scholar
  49. 49.
    Karbalay-Doust S, Noorafshan A (2006) Stereological study of the effects of nandrolone decanoate on the rat prostate. Micron 37:617–623CrossRefGoogle Scholar
  50. 50.
    Signoretti S, Waltregny D, Dilks J, Isaac B, Lin D, Garraway L, Yang A, Montironi R, McKeon F, Loda M (2000) p63 is a prostate basal cell marker and is required for prostate development. Am J Pathol 157:1769–1775CrossRefGoogle Scholar
  51. 51.
    Chang HH, Chen BY, Wu CY, Tsao ZJ, Chen YY, Chang CP, Yang CR, Lin DP (2011) Hedgehog overexpression leads to the formation of prostate cancer stem cells with metastatic property irrespective of androgen receptor expression in the mouse model. J Biomed Sci 18:6. doi: 10.1186/1423-0127-18-6 CrossRefGoogle Scholar
  52. 52.
    Parr MK, Blatt C, Zierau O, Hess C, Gütschow M, Fusshöller G, Opfermann G, Schänzer W, Diel P (2011) Endocrine characterization of the designer steroid methyl-1-testosterone: investigations on tissue-specific anabolic-androgenic potency, side effects, and metabolism. Endocrinology 152:4718–4728CrossRefGoogle Scholar
  53. 53.
    Bonkhoff H, Fixemer T (2005) Implications of estrogens and their receptors for the development and progression of prostate cancer. Pathologe 26:461–468CrossRefGoogle Scholar
  54. 54.
    Weihua Z, Makela S, Andersson LC, Salmi S, Saji S, Webster JI, Jensen EV, Nilsson S, Warner M, Gustafsson JA (2001) A role for estrogen receptor β in the regulation of growth of the ventral prostate. PNAS 98:6330–6335CrossRefGoogle Scholar
  55. 55.
    Weihua Z, Lathe R, Warner M, Gustafsson JA (2002) An endocrine pathway in the prostate, ERβ, AR, 5α-androstane-3β, 17β-diol, and CYP7B1, regulates prostate growth. PNAS 99:13589–13594CrossRefGoogle Scholar
  56. 56.
    Gebara OCE, Vieira NW, Meyer JW, Calich ALG, Tai EJ, Pierri H, Wajngarten M, Aldrighi JM (2002) Cardiovascular effects of testosterone. Arq Bras Cardiol 79:644–649CrossRefGoogle Scholar
  57. 57.
    Alphonse P, Aluko R (2015) A review on the anti-carcinogenic and anti-metastatic effects of flax seed lignan secolariciresinol diglucoside (SDG). Discov Phytomed 2(2):12–17CrossRefGoogle Scholar
  58. 58.
    Cardozo LF, Boaventura GT, Brant LH, Pereira VA, Velarde LG, Chagas MA (2012) Prolonged consumption of flaxseed flour increases the 17β-estradiol hormone without causing adverse effects on the histomorphology of Wistar rats’ penis. Food Chem Toxicol 50(11):4092–4096CrossRefGoogle Scholar
  59. 59.
    Ruhlen RL, Howdeshell KL, Mao J, Taylor JA, Bronson FH, Newbold RR, Welshons WV, vom Saal FS (2008) Low phytoestrogen levels in feed increase fetal serum estradiol resulting in the “fetal estrogenization syndrome” and obesity in CD-1 mice. Environ Health Perspect 116(3):322–328CrossRefGoogle Scholar
  60. 60.
    Troina AA, Figueiredo MS, Moura EG, Boaventura GT, Soares LL, Cardozo LF, Oliveira E, Lisboa PC, Passos MA, Passos MC (2010) Maternal flaxseed diet during lactation alters milk composition and programs the offspring body composition, lipid profile and sexual function. Food Chem Toxicol 48(2):697–703CrossRefGoogle Scholar
  61. 61.
    Ellem SJ, Risbridger GP (2009) The dual, opposing roles of estrogen in the prostate. Ann N Y Acad Sci 1155:174–186CrossRefGoogle Scholar
  62. 62.
    Lin X, Gingrich JR, Bao W, Li J, Haroon ZA, Demark-Wahnefried W (2002) Effect of flaxseed supplementation on prostatic carcinoma in transgenic mice. Urology 60:919–924CrossRefGoogle Scholar
  63. 63.
    Costa WS, de Carvalho AM, Babinski MA, Chagas MA, Sampaio FJ (2004) Volumetric density of elastic and reticular fibers in transition zone of controls and patients with benign prostatic hyperplasia. Urology 64(4):693–697CrossRefGoogle Scholar
  64. 64.
    Vilamaior PS, Felisbino SL, Taboga SR, Carvalho HF (2000) Collagen fiber reorganization in the rat ventral prostate following androgen deprivation: a possible role for smooth muscle cells. Prostate 45:253–258CrossRefGoogle Scholar
  65. 65.
    Rubinstein M, Sampaio FJ, Costa WS (2007) Stereological study of collagen and elastic system in the detrusor muscle of bladders from controls and patients with infravesical obstruction. Int Braz J Urol 33:33–41CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Ilma Cely de Amorim Ribeiro
    • 1
  • Carlos Alberto Soares da Costa
    • 2
  • Vivian Alves Pereira da Silva
    • 1
  • Lanna Beatriz Neves Silva Côrrea
    • 1
  • Gilson Teles Boaventura
    • 2
  • Mauricio Alves Chagas
    • 1
    Email author
  1. 1.Department of Morphology, Laboratory of Cellular and Extracellular Biomorphology Biomedic InstituteFederal Fluminense UniversityRio de JaneiroBrazil
  2. 2.Department of Nutrition and Dietetics, Experimental Nutrition Laboratory, College of NutritionFederal Fluminense UniversityRio de JaneiroBrazil

Personalised recommendations