Main Article Content
Polycystic ovary syndrome (PCOS) is one of the most common reproductive and endocrine disorders in women of reproductive age. This study was commenced to elucidate the efficacy of melatonin in the pathogenesis of letrozole induced (PCOS) in Wistar rats. For this study albino rats were treated with Letrozole orally (1mg/kg) to induce PCOS condition. Total 24 rats were randomly selected for the experimental purpose and were divided into four groups viz. group I served as normal control, group II served as letrozole treated, group III served as melatonin treated and group IV served as letrozole and Melatonin treated.
On the completion of experimental period of 35 days, animals were sacrificed. Ovaries of all respective groups were dissected out and processed for the assessment of biochemical variables viz. lipid peroxidation (LPO), antioxidative system; superoxide dismutase (SOD), reduced glutathione (GSH) and Catalase (CAT) activity, total protein quantification and lipid parameters (Total Cholesterol, Triglycerides, high density lipids, low density lipids and very low density lipids). Letrozole administration in group II led to significant increase in lipid peroxidation, total protein content and lipid profile and a significant decrease in antioxidant activity. However, administration of melatonin in group IV resulted in the recovery of these parameters significantly towards the normal comparable to the control group. Therefore, melatonin might be suggested as a protective molecule against letrozole induced PCOS condition.
Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat. Rev. Endocrinol. 2011;7:219-231.
Pasquali R, Stener‐Victorin E, Yildiz BO, Duleba AJ, Hoeger K, Mason H, Homburg R, Hickey T, Franks S, Tapanainen JS, Balen A. PCOS Forum: research in polycystic ovary syndrome today and tomorrow. Clin. Endocrinol. 2011;74:424-433.
Zawadzki J, Dunaif A. PCOS Forum: research in polycystic ovary syndrome today and tomorrow. PCOS. 1992;4:377–84.
Skrtic A, Sokolic L, Borovecki A, Rosa J, Fenzl V. Immunohistochemical localization of CD31, NOTCH1 and JAGGED1 proteins in experimentally induced polycystic ovaries of immature rats. Acta Histochem. 2011;113:262-269.
Baravalle C, Salvetti NR, Mira GA, Pezzone N, Ortega HH. Microscopic characterization of follicular structures in letrozole-induced polycystic ovarian syndrome in the rat. Arch. Med. Res. 2006;37:830-839.
Dasgupta S, Reddy BM. Present status of understanding on the genetic etiology of polycystic ovary syndrome. J. Postgrad. Med. 2008;54:114-125.
Guttmann-Bauman I. Approach to adolescent polycystic ovary syndrome (PCOS) in the pediatric endocrine community in the USA. J. Pediatr. Endocrinol. Metab. 2005;18:499-506.
Huang, J, Ni R, Chen X, Huang L, Mo Y, Yang D. Metabolic abnormalities in adolescents with polycystic ovary syndrome in south China. Reprod. Biol. Endocrinol. 2010;8:142.
Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF. Criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. J. Clin. Endocrinol. Metab. 2006;91:4237-4245.
Srivastava RK, Krishna A. Pathophysiology of polycystic ovary syndrome (PCOS): lessons from animal studies. Proc. India Natl. Sci. Acad. 2006;B71:191-205.
Fisher CR, Graves KH, Parlow AF, Simpson ER. Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene. Proc. Natl. Acad. Sci. U.S.A. 1998;95:6965-6970.
Kafali H, Iriadam M, Ozardalı I, Demir N. Letrozole-induced polycystic ovaries in the rat: A new model for cystic ovarian disease. Arch. Med. Res. 2004;35:103-108.
Rai S, Basheer M, Ghosh H, Acharya D, Hajam YA. Melatonin attenuates free radical load and reverses histologic architect and hormone profile alteration in female rat: An. In vivo study of pathogenesis of letrozole induced poly cystic ovary. J. Clin. Cell. Immunol. 2015;6:384. DOI:10.4172/2155-9899.1000384.
Reichlin S. The pineal gland. In: Wilson JD & Foster D (Editors), Williams Textbook of Endocrinology. (8th edn), WB Saunders company, Philadelphia, USA. 1992;240-253.
Djeridane Y, Vivien‐Roels B, Simonneaux V, Miguez JM, Pévet P. Evidence for melatonin synthesis in rodent Harderian gland: a dynamic in vitro study. J. Pineal Res. 1998;25:54-64.
Tan DX, Reiter RJ, Manchester LC, Yan MT, El-Sawi M, Sainz RM, Mayo JC, Kohen R, Allegra MC, Hardeland R. Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Curr. Top. Med. Chem. 2002;2:181-197.
Reiter RJ, Mayo JC, Tan DX, Sainz RM, Alatorre‐Jimenez M, Qin L. Melatonin as an antioxidant: under promises but over delivers. J. Pineal Res. 2016;61:253–278.
Pappolla MA, Chyan YJ, Poeggeler B, Frangione B, Wilson G, Ghiso J, Reiter RJ. An assessment of the antioxidant and the antiamyloidogenic properties of melatonin: Implications for Alzheimer's disease. J. Neural Transm. 2000;107:203-231.
Bonilla E, Valero N, Chacín‐Bonilla L, Medina‐Leendertz S. Melatonin and viral infections. J. Pineal Res. 2004;36:73-79.
Hussain SA, Khadim HM, Khalaf BH, Ismail SH, Hussein KI, Sahib AS. Effects of melatonin and zinc on glycemic control in type 2 diabetic patients poorly controlled with metformin. Saudi Med. J. 2004;27:1483-1488.
Lissoni P. Biochemotherapy with standard chemotherapies plus the pineal hormone melatonin in the treatment of advanced solid neoplasms. Pathol. Biol. 2007;55:201-204.
Bilal A, Jahan N, Ahmed A, Bilal SN, Habib S. Antifertility Activity of Hydroalcoholic Extract of Ocimum basilicum Linn. Leaves on Female Wistar Rats. J. Reprod. Contracept. 2013;24:45-54.
Lowry OH, Rosebrough NJ, Farr AL, Randall R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 1951;193:265-275.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 1979;95:351-358.
Sadlak J, Raymond HL. Estimation of total thiol, protein bound and non-protein sulfhydryl groups in tissue with ellman’s reagent. Anal. Biochem. 1968;25:192-132.
Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay. Indian J. Biochem. Biophys. 1984;21:130-132.
Beers RF Sizer IW. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J. Biol. Chem. 1952;195:133-140.
Cardinali DP, Rosner JM. Ocular distribution of hydroxyindole-O-methyl transferase (HIOMT) in the duck (Anas platyrhinchos), Gen. Comp. Endocrinol. 1972;18(2):407–409.
Quay WB. Humoral interrelations of the pineal gland with lateral eyes and orbital glands. The Pineal Gland and its Endocrine Role, Springer, Boston, MA. 1983;395–416.
Djeridane Y, Vivien-Roels B, Simonneaux V, Miguel JM, Pevet P. Evidence for melatonin in rodent Harderian gland: A dynamic in vitro study, J. Pineal Res. 1998; 25(1):54–64.
Allegra M, Reiter RJ, Tan DX, Gentile C, Tesoriere L, Livrea MA. The chemistry of melatonin's interaction with reactive species. J. Pineal Res. 2003;34(1):1–10.
Reiter RJ, Mayo JC, Tan DX, Sainz RM, Alatorre-Jimenez M, Qin L. Melatonin as an antioxidant: under promises but over delivers, J. Pineal Res. 2016;61(3):253–278.
Manneras L, Cajander S, Holmang A, Seleskovic Z, Lystig T, Lonn M, Stener-Victorin E. A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome. Endocrinology. 2007;148:3781-3791.
Oktenli C, Ozgurtas T, Dede M, Sanisoglu YS, Yenen MC, Yesilova Z, Kenar L, Kurt YG, Baser I, Smith J, Cianflone K. Metformin decreases circulating acylation-stimulating protein levels in polycystic ovary syndrome. Gynecol. Endocrinol. 2007;23:710-715.
Korkina LG, Afanas’ev IB. Advances in pharmacology. 1996;38:151–63.
Sabuncu T, Vural H, Harma M, Harma M. Oxidative stress in polycystic ovary syndrome and its contribution to the risk of cardiovascular disease. Clin. Biochem. 2011;34:407-413.
Liu J, Zhang D. The role of oxidative stress in the pathogenesis of polycystic ovary syndrome. Sichuan da xue xue bao. Yi xue ban= Journal of Sichuan University. Medical Science Edition. 2012; l43:187-190.
Jahan S, Munir F, Razak S, Mehboob A, Ain QU, Ullah H, Afsar T, Shaheen G, Almajwal A. Ameliorative effects of rutin against metabolic, biochemical and hormonal disturbances in polycystic ovary syndrome in rats. J. Ovarian Res. 2016;9:86.
Reddy PS, Begum N, Mutha S, Bakshi V. Beneficial effect of Curcumin in Letrozole induced polycystic ovary syndrome. Asian Pac. J. Reprod. 2016;5:116-122.
Ayala A, Munoz MF, Arguelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid. Med. Cell. Longev. Article ID 360438. 2014;31. DOI:10.1155/2014/360438.
Hajam YA, Rai S, Roy A, Basheer M, Ghosh H. Repossession of brain complications in a streptozotocin induced diabetic rat by exogenous melatonin administration. Int. J. Zool. Res. 2017;13:64-73.
Haldar C, Singh SS. Seasonal changes in melatonin and immunological adaptation in birds. J. Endocrinol. Reprod. 2011;5: 13–24.