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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Iodine Bonded with Milk Protein Inhibits Benign Prostatic Hyperplasia Development in Rats

Author(s): Vladimir G. Bespalov*, Valerii A. Alexandrov, Grigory V. Tochilnikov, Dmitrii Е. Lukin, Nadezhda T. Zhilinskaya, Alexandr L. Semenov, Irina N. Vasilyeva, Vladimir A. Romanov, Irina A. Tumanyan, Elena D. Ermakova, Elizaveta I. Kovalevskaya, ">Nadezhda V. Barakova and ">Denis A. Baranenko

Volume 19, Issue 13, 2019

Page: [1627 - 1632] Pages: 6

DOI: 10.2174/1871520619666190705143927

Price: $65

Abstract

Background: There is some evidence that Benign Prostatic Hyperplasia (BPH) may increase the risk of developing prostate cancer, so conducting research on effective BPH inhibitors is important.

Objective: This research studied the inhibitory effect of Iodized Serum Milk Protein (ISMP) on BPH in rats. ISMP is a concentrate of lactic protein containing 2.2% iodine.

Methods: Male Wistar rats, aged 18 months, were used. In the intact control group, sunflower oil was administered intragastrically by gavage. In 36 rats, BPH was induced by surgical castration, followed by subcutaneous injections of prolonged testosterone - omnadren, 25mg/kg every other day (7 administrations). One group of rats served as BPH-control. ISMP and finasteride (positive control), dissolved in sunflower oil, were administered to rats intragastrically daily at a dose of 200μg/kg and 5mg/kg, respectively, for 4 weeks starting immediately after castration.

Results: ISMP inhibited the development of BPH in rats, significantly reducing the mass of the prostate and its parts (except for the anterior lobes) by 1.1-1.3 times and the prostatic index (the ratio of prostate weight to the body weight) - by 1.3-1.4 times. Finasteride inhibited the development of BPH, and its activity was higher (by 1.1-1.3 times) than in ISMP.

Histological analysis of the prostate showed fewer pronounced morphological hyperplasia signs in animals treated with ISMP or finasteride.

Conclusion: The iodine-containing preparation ISMP has the ability to inhibit the development of BPH in rats although its activity is somewhat lower than that of finasteride.

Keywords: Prostatic hyperplasia, inhibition, iodine, milk protein, iodotyrosines, finasteride.

Graphical Abstract
[1]
Bostwick, D.G.; Cooner, W.H.; Denis, L.; Jones, G.W.; Scardino, P.T.; Murphy, G.P. The association of benign prostatic hyperplasia and cancer of the prostate. Cancer, 1992, 70(Suppl. 1), 291-301.
[2]
Alcaraz, A.; Hammerer, P.; Tubaro, A.; Schröder, F.H.; Castro, R. Is there evidence of a relationship between benign prostatic hyperplasia and prostate cancer? Findings of a literature review. Eur. Urol., 2009, 55(4), 864-873.
[3]
Ørsted, D.D.; Bojesen, S.E. The link between benign prostatic hyperplasia and prostate cancer. Nat. Rev. Urol., 2013, 10(1), 49-54.
[4]
Miah, S.; Catto, J. BPH and prostate cancer risk. Indian J. Urol., 2014, 30(2), 214-218.
[5]
Bespalov, V.G.; Kuzhanov, A.A.; Vasilieva, I.N.; Semenov, A.L.; Alexandrov, V.A. Relationship between benign prostatic hyperplasia and prostate cancer: New opportunities for prostate cancer chemoprevention. Vopr. Onkol., 2016, 62(2), 360-371.
[6]
Chokkalingam, A.P.; Nyrén, O.; Johansson, J.E.; Gridley, G.; McLaughlin, J.K.; Adami, H.O.; Hsing, A.W. Prostate carcinoma risk subsequent to diagnosis of benign prostatic hyperplasia: A population-based cohort study in Sweden. Cancer, 2003, 98(8), 1727-1734.
[7]
Ørsted, D.D.; Bojesen, S.E.; Nielsen, S.F.; Nordestgaard, B.G. Association of clinical benign prostate hyperplasia with prostate cancer incidence and mortality revisited: A nationwide cohort study of 3, 009, 258 men. Eur. Urol., 2011, 60(4), 691-698.
[8]
Jun, J.E.J.; Kinkade, A.; Tung, A.C.H.; Tejani, A.M. 5α-Reductase inhibitors for treatment of benign prostatic hyperplasia: A systematic review and meta-analysis. Can. J. Hosp. Pharm., 2017, 70(2), 113-119.
[9]
Thompson, I.M.; Klein, E.A.; Lippman, S.M.; Coltman, C.A.; Djavan, B. Prevention of prostate cancer with finasteride: US/European perspective. Eur. Urol., 2003, 44(6), 650-655.
[10]
Andriole, G.L.; Bostwick, D.G.; Brawley, O.W.; Gomella, L.G.; Marberger, M.; Montorsi, F.; Pettaway, C.A.; Tammela, T.L.; Teloken, C.; Tindall, D.J.; Somerville, M.C.; Wilson, T.H.; Fowler, I.L.; Rittmaster, R.S. REDUCE Study Group. Effect of dutasteride on the risk of prostate cancer. N. Engl. J. Med., 2010, 362(13), 1192-1202.
[11]
Aceves, C.; Anguiano, B.; Delgado, G. The extrathyronine actions of iodine: antioxidant, apoptotic and differentiator factor in iodine uptake tissues. Thyroid, 2013, 23(8), 938-946.
[12]
De la Vieja, A.; Santisteban, P. Role of iodide metabolism in physiology and cancer. Endocr. Relat. Cancer, 2018, 25(4), 225-245.
[13]
Nakatsuka, H.; Chiba, K.; Watanabe, T.; Sawatari, H.; Seki, T. Iodine intake by adult residents of a farming area in Iwate Prefecture, Japan, and the accuracy of estimated iodine intake calculated using the standard tables of food composition in Japan. Environ. Health Prev. Med., 2016, 21(6), 523-530.
[14]
Katagiri, R.; Asakura, K.; Sasaki, S.; Hirota, N.; Notsu, A.; Miura, A.; Todoriki, H.; Fukui, M.; Date, C. Estimation of habitual iodine intake in Japanese adults using 16 d diet records over four seasons with a newly developed food composition database for iodine. Br. J. Nutr., 2015, 114(4), 624-634.
[15]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[16]
Savchik, S.A.; Zhukova, G.F.; Lublinskii, S.L. The study of physico-chemical properties of iodinated proteins for iodine deficiency prophylaxis. Vopr. Pitan., 2005, 74(4), 3-8.
[17]
Scolnik, M.D.; Servadio, C.; Abramovici, A. Comparative study of experimentally induced benign and atypical hyperplasia in the ventral prostate of different rat strains. J. Androl., 1994, 15(4), 287-297.
[18]
Kulikovskii, A.V.; Lisitsyn, A.B.; Chernukha, I.M.; Gorlov, I.F.; Savchuk, S.A. Determination of iodotyrosines in food. J. Anal. Chem., 2016, 71(12), 1215-1219.
[19]
Bolshakova, L.S.; Lisitsyn, A.B.; Chernukha, I.M.; Zubtsov, Y.N.; Lukin, D.E.; Lyublinsky, S.L. The study of the metabolism of iodotyrosines included in the iodized milk protein in rats. Vopr. Pitan., 2018, 87(4), 12-17.
[20]
Quintero-García, M.; Delgado-González, E.; Sánchez-Tusie, A.; Vázquez, M.; Aceves, C.; Anguiano, B. Iodine prevents the increase of testosterone-induced oxidative stress in a model of rat prostatic hyperplasia. Free Radic. Biol. Med., 2018, 115, 298-308.
[21]
Minciullo, P.L.; Inferrera, A.; Navarra, M.; Calapai, G.; Magno, C.; Gangemi, S. Oxidative stress in benign prostatic hyperplasia: A systematic review. Urol. Int., 2015, 94(3), 249-254.
[22]
Roumeguère, T.; Sfeir, J.; El Rassy, E.; Albisinni, S.; Van Antwerpen, P.; Boudjeltia, K.Z.; Farès, N.; Kattan, J.; Aoun, F. Oxidative stress and prostatic diseases. Mol. Clin. Oncol., 2017, 7(5), 723-728.
[23]
Navarra, M.; Micali, S.; Lepore, S.M.; Cesinaro, A.M.; Celano, M.; Sighinolfi, M.C.; De Gaetani, C.; Filetti, S.; Bianchi, G.; Russo, D. Expression of the sodium/iodide symporter in human prostate adenocarcinoma. Urology, 2010, 75(4), 773-778.
[24]
Aranda, N.; Sosa, S.; Delgado, G.; Aceves, C.; Anguiano, B. Uptake and antitumoral effects of iodine and 6-iodolactone in differentiated and undifferentiated human prostate cancer cell lines. Prostate, 2013, 73(1), 31-41.
[25]
Olvera-Caltzontzin, P.; Delgado, G.; Aceves, C.; Anguiano, B. Iodine uptake and prostate cancer in the TRAMP mouse model. Mol. Med., 2013, 19, 409-416.
[26]
Gupta, S.; Adhami, V.M.; Subbarayan, M.; MacLennan, G.T.; Lewin, J.S.; Hafeli, U.O.; Hafeli, U.O.; Fu, P.; Mukhtar, H. Suppression of prostate carcinogenesis by dietary supplementation of celecoxib in transgenic adenocarcinoma of the mouse prostate model. Cancer Res., 2004, 64(9), 3334-3343.
[27]
Bonorden, M.J.; Grossmann, M.E.; Ewing, S.A.; Rogozina, O.P.; Ray, A.; Nkhata, K.J.; Liao, D.J.; Grande, J.P.; Cleary, M.P. Growth and progression of TRAMP prostate tumors in relationship to diet and obesity. Prostate Cancer, 2012, 2012543970
[28]
Nguewa, P.A.; Calvo, A. Use of transgenic mice as models for prostate cancer chemoprevention. Curr. Mol. Med., 2010, 10(8), 705-718.
[29]
Xu, K.; Ling, M.T.; Wang, X.; Wong, Y.C. Evidence of a novel biomarker, alphas1-Casein, a milk protein, in benign prostate hyperplasia. Prost Cancer Prostatic Dis., 2006, 9(3), 293-297.
[30]
HoptionCann. S.A.; Qiu, Z.; van Netten, C. A prospective study of iodine status, thyroid function, and prostate cancer risk: Follow-up of the first national health and nutrition examination survey. Nutr. Cancer, 2007, 58(1), 28-34.

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