Indole-based derivatives effect on rats with polycystic ovary syndrome

Journal of Pharmaceutical Investigation - Tập 47 - Trang 439-444 - 2017
Parichehreh Yaghmaei1, Babak Dehestani2, Samira Ghorbani1, Farzaneh Abbasi3, Azadeh Ebrahim-Habibi4
1Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
2Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
3Growth and Development Research Center, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
4Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Shariati Hospital, Tehran, Iran

Tóm tắt

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age, for which efficient therapies are needed. In this study, PCOS was induced in rats by intraperitoneal administration of testosterone propionate (0.2 mg/kg). Indole-based compounds 5-hydroxy indole-2-carboxylic acid, N-acetyl-tryptophan, Tryptamine, l-Tryptophan and Tryptophol were administered for 8 weeks in the PCOS model, after what histopathological assessment of ovaries was performed. The number of primary follicles, corpus luteum, growing follicles and graafian follicles increased and the number and diameter of ovarian cysts decreased in all treated rats in comparison with untreated group. In conclusion, l-Tryptophan and Tryptophol were most efficient as potential therapeutic molecules.

Tài liệu tham khảo

Barfield E, Liu YH, Kessler M, Pawelczak M, David R, Shah B (2009) The prevalence of abnormal liver enzymes and metabolic syndrome in obese adolescent females with polycystic ovary syndrome. J Pediatr Adolesc Gynecol 22:318–322 Ehrmann DA (2005) Polycystic ovary syndrome. N Engl J Med 352:1223–1236 Galano A, Tan DX, Reiter RJ (2011) Melatonin as a natural ally against oxidative stress: a physicochemical examination. J Pineal Res 51:1–16 Güney M, Oral B, Karahan N, Mungan T (2008) Regression of endometrial explants in a rat model of endometriosis treated with melatonin. Fertil Steril 89:934–942 Hardeland R, Pandi-Perumal SR, Cardinali DP (2006) Melatonin. Int J Biochem Cell Biol 38:313–316 Klerman H, St Hilaire MA, Kronauer RE, Gooley JJ, Gronfier C, Hull JT, Lockley SW, Santhi N, Wang W, Klerman EB (2012) Analysis method and experimental conditions affect computed circadian phase from melatonin data. PLoS ONE 7(4):e33836 Mills E, Wu P, Seely D, Guyatt G (2005) Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res 39:360–366 Moreira S, Soares E, Tomaz G, Maranhão T, Azevedo G (2010) Polycystic ovary syndrome: a psychosocial approach. Acta Med Port 23:237–242 Niles LP, Wang J, Shen L, Lobb DK, Younglai EV (1999) Melatonin receptor mRNA expression in human granulosa cells. Mol Cell Endocrinol 156:107–110 Pai SA, Majumdar AS (2014) Protective effects of melatonin against metabolic and reproductive disturbances in polycystic ovary syndrome in rats. J Pharm Pharmacol 66:1710–1721 Plachot M, Belaisch-Allart J, Mayenga JM, Chouraqui A, Tesquier A, Serkine AM, Boujenah A, Abirached F (2003) Oocyte and embryo quality in polycystic ovary syndrome. Gynecol Obstet Fertil 31:350–354 Prata Lima MF, Baracat EC, Simões MJ (2004) Effects of melatonin on the ovarian response to pinealectomy or continuous light in female rats: similarity with polycystic ovary syndrome. Braz J Med Biol Res 37:987–995 Richard DM, Dawes MA, Mathias CW, Acheson A, Hill-Kapturczak N, Dougherty DM (2009) l-Tryptophan: basic metabolic functions, behavioral research and therapeutic indications. Int J Tryptophan Res 2:45–60 Rivara S, Lorenzi S, Mor M, Plazzi PV, Spadoni G, Bedini A, Tarzia G (2005) Analysis of structure-activity relationships for MT2 selective antagonists by melatonin MT1 and MT2 receptor models. J Med Chem 48:4049–4060 Rosen J, Than NN, Koch D, Poeggeler B, Laatsch H, Hardeland R (2006) Interactions of melatonin and its metabolites with the ABTS cation radical: extension of the radical scavenger cascade and formation of a novel class of oxidation products, C2-substituted 3-indolinones. J Pineal Res 41:374–381 Ruan Z, Yang Y, Wen Y, Zhou Y, Fu X, Ding S, Liu G, Yao K, Wu X, Deng Z, Wu G, Yin Y (2014) Metabolomic analysis of amino acid and fat metabolism in rats with l-tryptophan supplementation. Amino Acids 46:2681–2691 Sam S, Dunaif A (2003) Polycystic ovary syndrome: syndrome XX? Trends Endocrinol Metab 14:365–370 Shirinzadeh H, Eren B, Gurer-Orhan H, Suzen S, Ozden S (2010) Novel indole-based analogs of melatonin: synthesis and in vitro antioxidant activity studies. Molecules 15:2187–2202 Shreeve N, Cagampang F, Sadek K, Tolhurst M, Houldey A, Hill CM, Brook N, Macklon N, Cheong Y (2013) Poor sleep in PCOS; is melatonin the culprit? Hum Reprod 28:1348–1353 Soares JM, Masana MI, Erşahin C, Dubocovich ML (2003) Functional melatonin receptors in rat ovaries at various stages of the estrous cycle. J Pharmacol Exp Ther 306:694–702 Srinivasan V, Spence DW, Pandi-Perumal SR, Trakht I, Cardinali DP (2008) Therapeutic actions of melatonin in cancer: possible mechanisms. Integr Cancer Ther 7:189–203 Suzen S (2013) Melatonin and synthetic analogs as antioxidants. Curr Drug Deliv 10:71–75 Suzen S, Tekiner-Gulbas B, Shirinzadeh H, Uslu D, Gurer-Orhan H, Gumustas M, Ozkan SA (2013) Antioxidant activity of indole-based melatonin analogues in erythrocytes and their voltammetric characterization. J Enzyme Inhib Med Chem 28:1143–1155 Tamura H, Nakamura Y, Korkmaz A, Manchester LC, Tan DX, Sugino N, Reiter RJ (2009) Melatonin and the ovary: physiological and pathophysiological implications. Fertil Steril 92:328–343 Tanavde VS, Maitra A (2003) In vitro modulation of steroidogenesis and gene expression by melatonin: a study with porcine antral follicles. Endocr Res 29:399–410 Tyndall V, Broyde M, Sharpe R, Welsh M, Drake AJ, McNeilly AS (2012) Effect of androgen treatment during foetal and/or neonatal life on ovarian function in prepubertal and adult rats. Reproduction 143:21–33 Vassilatou E, Lafoyianni S, Vryonidou A, Ioannidis D, Kosma L, Katsoulis K, Papavassiliou E, Tzavara I (2010) Increased androgen bioavailability is associated with non-alcoholic fatty liver disease in women with polycystic ovary syndrome. Hum Reprod 25:212–220 Yanes LL, Romero DG, Moulana M, Lima R, Davis DD, Zhang H, Lockhart R, Racusen LC, Reckelhoff JF (2011) Cardiovascular-renal and metabolic characterization of a rat model of polycystic ovary syndrome. Gend Med 8:103–115