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Manuscript ID : ASCIJ-2207-1404 (R1) Visit : 304 Page: 105 - 119

10.22034/ascij.2022.1963114.1404

Article Type: Original Research

Effect of Atorvastatin on the Levels of Sex Hormones and Oxidative Stress Index in Letrozole-induced Polycystic Ovary Syndrome in Adult Female Wistar Rats

Subject Areas : Journal of Animal Biology

Shamsi Zavari 1 , Akram Eidi 2 , Pejman Mortazavi 3 , Shahrbanoo Oryan 4

1 - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
2 - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
3 - Department of Veterinary, Science and Research Branch, Islamic Azad University, Tehran, Iran
4 - Department of Biology, Faculty of Biology Science, Kharazmi University, Tehran

Received: 2022-07-16 Accepted : 2022-10-31 Published : 2023-05-22

Keywords: Rat, Letrozole, PCOs, Atorvastatin,

Abstract :

Atorvastatin is currently one of the most commonly used drugs in the clinics for the treatment of coronary heart disease and is mainly used for the control of risk factors in coronary heart disease as well as in the improvement of prognosis. Polycystic ovary syndrome (PCOS) is a prevalent endocrinological disorder in reproductive-age women and is often associated with metabolic syndrome. In the present study, the effect of atorvastatin on letrozole-induced PCOS was investigated in adult female Wistar rats. The rats were randomly divided into 8 groups: normal control, atorvastatin (10, 50, and 100 mg/kg intragastrically, daily) alone, PCOS control rats (letrozole, 1 mg/kg, intragastrically, daily), atorvastatin (10, 50, and 100 mg/kg intragastrically, daily) together with (letrozole1 mg/kg, intragastrically, daily), and administration was performed accordingly. Administration of atorvastatin was started 30 min. before the first dose of letrozole and continued for up to 30 days. The animals were euthanized 24 h after the last dose of the administration. Blood samples were collected by cardiac puncture. Serum was separated and evaluated for determination of estradiol, LH, FSH, and testosterone levels. Moreover, antioxidant activity was tested by measuring using superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and malondialdehyde (MDA) levels in ovary homogenate. Our results showed that the administration of atorvastatin significantly improved PCOS-induced hormonal impairment. Also, the administration of atorvastatin increased the levels of antioxidant enzymes, including SOD, CAT, and GPX, while decreasing MDA levels. Taken together, the results of this study suggest that atorvastatin administration may be beneficial in letrozole-induced PCOS in rats. s.

References:


  1. Adibmoradi M., Morovvati H., Moradi H.R., Sheybani M.T., Amoli J.S., Mazaheri Nezhad Fard R. 2015. Protective effects of wheat sprout on testicular toxicity in male rats exposed to lead. Reproductive System and Sex Disorders, 4(4):1-9.
    2.
  2. Alizadeh F., Azarnia M., Mirabolghasemi G., Karampoor P. 2015. Effect of fruit heracleum persicum extract on changes in serum levels of sex hormones in rats with polcystic ovary syndrome (PCOS). Armaghane Danesh, 20(1):31-42.
    3.
  3. Al-Zaid M, Towers P, Scott C, Al-Shoumer K. 2005. Ovarian steroids modulate neuroendocrine dysfunction in polycystic ovary syndrome. Journal of Endocrinological Investigation, 28(1):882-892.
    4.
  4. Azziz R. 2018. Polycystic ovary syndrome. Obstetrics and Gynecology, 132(2):321-336.
    5.
  5. Baillargeon J.P. 2005. Use of insulin sensitizers in polycystic ovarian syndrome. Current Opinion in Investigational Drugs, 6(10):1012-1022.
    6.
  6. Bendich A., Papas A.M. 1999. Book Review-//Antioxidant status, diet, nutrition, and health. Free Radical Biology and Medicine, 27(1):241.
    7.
  7. Bosek P., Nakano M. 2003. Hepatoprotective effect of rooibos tea (Aspalathus linearis) on CCl 4-induced liver damage in rats. Physiological Research, 52(4):461-466.
    8.
  8. Çiftçi G.A., Ertorun İ., Akalin A., Alataş İ.Ö., Musmul A. 2015. The effects of atorvastatin on antioxidant/ antiinflammatory propertiesof HDLs in hypercholesterolemics. Turkish Journal of Medical Sciences, 45(2):345-351.
    9.
  9. Duleba A.J. 2012. Medical management of metabolic dysfunction in PCOS. Steroids, 77(4):306-311.
    10.
  10. Engmann L., Siano L., Schmidt D., Nulsen J., Maier D., Benadiva C. 2006. GnRH agonist to induce oocyte maturation during IVF in patients at high risk of OHSS. Reproductive Biomedicine Online, 13(5):639-644.
    11.
  11. Faghihi N., Mohammadi M.T., Salem F. 2015. Effect of atorvastatin on hyperglycemia-induced brain oxidative stress and neuropathy induced by diabetes. Journal of Birjand University of Medical Sciences, 22(1):48-58.
    12.
  12. Fenkci V., Fenkci S., Yilmazer M., Serteser M. 2003. Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertility and Sterility, 80(1):123-127.
    13.
  13. Gong X., Ma Y., Ruan Y., Fu G., Wu S. 2014. Long-term atorvastatin improves age-related endothelial dysfunction by ameliorating oxidative stress and normalizing eNOS/iNOS imbalance in rat aorta. Experimental Gerontology, 52:9-17.
    14.
  14. Gundapaneni K.K., Shyamala N., Galimudi R.K., Sahu S.K., Hanumanth S.R. 2016. A therapeutic effects of atorvastatin on genetic damage in coronary artery disease. Journal of Clinical and Diagnostic Research, 10(6):OC28.
    15.
  15. Horie K., Takakura K., Fujiwara H., Suginami H., Liao S., Mori T. 1992. Immunohistochemical localization of androgen receptor in the human ovary throughout the menstrual cycle in relation to oestrogen and progesterone receptor expression. Human Reproduction, 7(2):184-190.
    16.
  16. Insenser M., Murri M., Del Campo R., Martinez-Garcia M.A., Fernandez-Duran E., Escobar-Morreale H.F. 2018. Gut microbiota and the polycystic ovary syndrome: influence of sex, sex hormones, and obesity. The Journal of Clinical Endocrinology and Metabolism, 103(7):2552-2562.
    17.
  17. Iuorno M.J., Nestler J.E. 2001. Insulin-lowering drugs in polycystic ovary syndrome. Obstetrics and Gynecology Clinics of North America, 28(1):153-164.
    18.
  18. Karimian M, Pourahmadi M, Jelodar G, Mehrab F, Mohammadi Z. 2013. The Effect of Atorvastatin on the Pancreatic Tissue of Male Rats. Armaghane Danesh, 18(1):44-49.
    19.
  19. Kocak F.E., Kucuk A., Ozyigit F., Tosun M., Kocak C., Kocak A. 2015. Protective effects of simvastatin administered in the experimental hepatic ischemia-reperfusion injury rat model. Journal of Surgical Research, 199(2):393-401.
    20.
  20. Koh K.K., Sakuma I., Quon M.J. 2011. Differential metabolic effects of distinct statins. Atherosclerosis, 215(1):1-8.
    21.
  21. Kuşçu N.K. Var A. 2009. Oxidative stress but not endothelial dysfunction exists in non-obese, young group of patients with polycystic ovary syndrome. Acta obstetricia et Gynecologica Scandinavica, 88(5):612-617.
    22.
  22. Laird M., Thomson K., Fenwick M., Mora J., Franks S., Hardy K. 2017. Androgen stimulates growth of mouse preantral follicles in vitro: interaction with follicle-stimulating hormone and with growth factors of the TGF β superfamily. Endocrinology, 158(4):920-935.
    23.
  23. Ludwig M., Finas D., Al-Hasani S., Diedrich K., Ortmann O. 1999. Oocyte quality and treatment outcome in intracytoplasmic sperm injection cycles of polycystic ovarian syndrome patients. Human Reproduction, 14(2):354-358.
    24.
  24. Macedo A.F., Taylor F.C., Casas J.P., Adler A., Prieto-Merino D., Ebrahim S. 2014. Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis. BMC Medicine, 12(1):1-13.
    25.
  25. Malhotra N., Gongadashetti K., Dada R., Singh N. 2014. Oxidative stress biomarkers in follicular fluid of women with PCOS and tubal factor infertility-is there a correaltion with in-vitro-fertilization outcome? Fertility and Sterility, 102(3):e86.
    26.
  26. Mehrabian F., Khani B., Kelishadi R., Ghanbari E. 2011. The prevalence of polycystic ovary syndrome in Iranian women based on different diagnostic criteria. Endokrynologia Polska, 62(3):238-242.
    27.
  27. Mohammadi M.T., Amini R., Jahanbakhsh Z., Shekarforoush S. 2013. Effects of atorvastatin on the hypertension-induced oxidative stress in the rat brain. Iranian Biomedical Journal, 17(3):152.
    28.
  28. Nabiuni M., Mohammadi S., Kayedpoor P., Karimzadeh L. 2015. The effect of curcumin on the estradiol valerate-induced polycystic ovary in rats. Feyz Journal of Kashan University of Medical Sciences, 18(6): 515-523.
    29.
  29. Okon M.A., Laird S.M., Tuckerman E.M., Li T.C. 1998. Serum androgen levels in women who have recurrent miscarriages and their correlation with markers of endometrial function. Fertility and Sterility, 69(4):682-690.
    30.
  30. Rafiei S., Edalatmanesh M.A. 2016. The effect of exercise training on serum level of β-Estradiol, testosterone, and cognitive deficit in rats with letrozole-induced polycystic ovary syndrome. Shefaye Khatam, 4(2):11-18.
    31.
  31. Reddy K.S. 2004. Cardiovascular disease in non-Western countries. New England Journal of Medicine, 350(24):2438-2440.
    32.
  32. Ruder E.H., Hartman T.J., Blumberg J., Goldman M.B. 2008. Oxidative stress and antioxidants: exposure and impact on female fertility. Human reproduction update, 14(4):345-357.
    33.
  33. Sabuncu T., Vural H., Harma M., Harma M. 2001. Oxidative stress in polycystic ovary syndrome and its contribution to the risk of cardiovascular disease. Clinical Biochemistry, 34(5):407-413.
    34.
  34. Saiyed A., Jahan N., Makbul S.A.A., Ansari M., Bano H., Habib S.H. 2016. Effect of combination of Withania somnifera Dunal and Tribulus terrestris Linn on letrozole induced polycystic ovarian syndrome in rats. Integrative Medicine Research, 5(4):293-300.
    35.
  35. Sasikala S., Shamila S. 2009. A novel Ayurvedic medicine-Asokarishtam in the treatment of letrozole induced pcos in rat. Journal of Cell and Tissue Research, 9(2):1903.
    36.
  36. Schachter M., Raziel A., Friedler S., Strassburger D., Bern O., Ron‐El R. 2003. Insulin resistance in patients with polycystic ovary syndrome is associated with elevated plasma homocysteine. Human Reproduction, 18(4):721-727.
    37.
  37. Sekhon L.H., Gupta S. Kim Y., Agarwal A. 2010. Female infertility and antioxidants. Current Women's Health Reviews, 6(2):84-95.
    38.
  38. Sheehan M.T. 2004. Polycystic ovarian syndrome: diagnosis and management. Clinical Medicine and Research, 2(1):13-27.
    39.
  39. Shen L.Y., Liang C.M., Yang W.J., Pan L., Li H., Hu H. 2018. Acupuncture treatment of polycystic ovarian syndrome patients with abdominal obesity by regulating dai meridian: a randomized controlled clinical trial. Zhen ci yan jiu: Acupuncture Research, 43(4):255-259.
    40.
  40. Speroff L., Fritz M. 2011. Clinical gynesology and infertility 8th edition. Philadelphia: Wolters Kluwer Lippincott Williams and Wilkins.
    41.
  41. Tsilchorozidou T., Overton C., Conway G.S. 2004. The pathophysiology of polycystic ovary syndrome. Clinical Endocrinology, 60(1):1-17.
    42.
  42. Vallejo-Vaz A.J., Fayyad R., Boekholdt S.M., Hovingh G.K., Kastelein J.J., Melamed S. 2018. Triglyceride-rich lipoprotein cholesterol and risk of cardiovascular events among patients receiving statin therapy in the TNT trial. Circulation, 138(8):770-781.
    43.
  43. Vasiljević M. 2000. The role of insulin and hyperinsulinemia in the pathogenesis of the polycystic ovary syndrome. Srpski Arhiv za Celokupno Lekarstvo, 128(9-10):335-339.
    44.
  44. Williams D., Feely J., 2002. Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clinical Pharmacokinetics, 41(5):343-370.
    45.
  45. Wu C., Lin F., Qiu S., Jiang Z. 2014. The characterization of obese polycystic ovary syndrome rat model suitable for exercise intervention. PloS One, 9(6):e99155.
    46.

 

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