Document Type : Original Article

Authors

1 Student Research Committee, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

2 Department of Anatomy, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

3 Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran

4 Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

Abstract

Background: Polycystic ovary syndrome (PCOS) is one the most common diseases in women in the fertility age. PCOS alters ovarian follicles and affects blood lipid profiles, liver enzymes and hormones. In this study, we tried to investigate the effects of coenzyme Q10 (CoQ10) on PCOS pathological conditions.
Methods: Twenty-four female rats were randomly divided into the three groups; 1: control group, 2: PCOS group (received 1 mg/ kg letrozole daily for 21 days, PO) and 3: PCOS + CoQ10 group (received 1 mg/kg letrozole with 10 mg/kg of CoQ10 for 21 days orally). Blood lipid profiles, liver enzymes, blood glucose and testosterone levels were measured and ovarian histopathology was evaluated.
Results: Histological examination showed reduced number of antral follicles in PCOS + CoQ10 group as compared with PCOS group (P<0.001). PCOS increased the alanine aminotransferase (ALT) enzyme by acting on the liver (P<0.01). Administration of CoQ10 during PCOS induction was able to reduce ALT levels (P<0.01). PCOS increased the cholesterol (P<0.05), fasting blood sugar (FBS) (P<0.05), triglyceride (P<0.001), low-density lipoprotein (LDL) (P<0.05) and testosterone levels (P<0.001) compared to the control group. However, CoQ10 treatment significantly reduced the above-mentioned parameters compared to the PCOS group.
Conclusion: The results of the present study confirm that CoQ10 has a therapeutic potential for PCOS-induced lipid and hormonal changes and ovarian tissue damages. CoQ10 supplementation and its concomitant use with letrozole could inhibit the development of PCOS in rats. Testosterone reduction could be an important mechanism for CoQ10 beneficial effects.

Highlights

Zahra Taghipour(Google scholar))((Pubmed)

 Iman Fatemi(Google scholar)(Pubmed)

Mahsa Hassanipour(Google scholar)(Pubmed)

Keywords

  1. 1. Azziz R, Carmina E, Chen Z, Dunaif A, Laven JS, Legro RS, et al. Polycystic ovary syndrome. Nat Rev Dis Primers. 2016;2:16057. doi: 10.1038/nrdp.2016.57.

    2. Gilbert EW, Tay CT, Hiam DS, Teede HJ, Moran LJ. Comorbidities and complications of polycystic ovary syndrome: An overview of systematic reviews. Clin Endocrinol (Oxf). 2018;89(6):683-99. doi: 10.1111/cen.13828.

    1. Navid S, Talebi A, Solhjoo S, Hadigol T, Saadatian Z, Noory P. Advances in stem cell therapy based on tissue engineering in the treatment of female infertility with a focus on POF. J Kerman Univ Med Sci. 2022;29(2):188-202. doi: 10.22062/ jkmu.2022.91899.

    2. Alahmadi AA, Alahmadi BA, Wahman LF, El-Shitany NA. Chamomile flower extract ameliorates biochemical and histological kidney dysfunction associated with polycystic ovary syndrome. Saudi J Biol Sci. 2021;28(11):6158-66. doi: 10.1016/j.sjbs.2021.06.066.

    3. Peng F, Hu Y, Peng S, Zeng N, Shi L. Apigenin exerts protective effect and restores ovarian function in dehydroepiandrosterone induced polycystic ovary syndrome rats: a biochemical and histological analysis. Ann Med. 2022;54(1):578-87. doi: 10.1080/07853890.2022.2034933.

    4. Jahan S, Abid A, Khalid S, Afsar T, Qurat Ul A, Shaheen G, et al. Therapeutic potentials of quercetin in management of polycystic ovarian syndrome using letrozole induced rat model: a histological and a biochemical study. J Ovarian Res. 2018;11(1):26. doi: 10.1186/s13048-018-0400-5.

    5. Pasquali R. Contemporary approaches to the management of polycystic ovary syndrome. Ther Adv Endocrinol Metab. 2018;9(4):123-34. doi: 10.1177/2042018818756790.

    6. Shirooie S, Khaledi E, Dehpour AR, Noori T, Khazaei M, Sadeghi F, et al. The effect of dapsone in testosterone enanthate-induced polycystic ovary syndrome in rat. J Steroid Biochem Mol Biol. 2021;214:105977. doi: 10.1016/j. jsbmb.2021.105977.

    7. Rashidi H, Ghaderian SB, Moradi L. The effect of vitamin D3 on improving lipid profile, fasting glucose and insulin resistance in polycystic ovary syndrome women with vitamin D deficiency. Middle East Fertil Soc J. 2018;23(3):178-83. doi: 10.1016/j.mefs.2017.11.002.

    8. Rashidi H, Tafazoli M, Jalali MT, Eghbalnejad Mofrad AM. Serum lipid profile and insulin resistance in women with polycystic ovary syndrome (PCOS). J Diabetes Metab Disord Control. 2018;5(3):148-52.

    9. Chen W, Pang Y. Metabolic syndrome and PCOS: pathogenesis and the role of metabolites. Metabolites. 2021;11(12):869. doi: 10.3390/metabo11120869.

    10. Wu G, Hu X, Ding J, Yang J. The effect of glutamine on dehydroepiandrosterone-induced polycystic ovary syndrome rats. J Ovarian Res. 2020;13(1):57. doi: 10.1186/s13048-020- 00650-7.

    11. Singeap AM, Stanciu C, Huiban L, Muzica CM, Cuciureanu T, Girleanu I, et al. Association between nonalcoholic fatty liver disease and endocrinopathies: clinical implications. Can J Gastroenterol Hepatol. 2021;2021:6678142. doi: 10.1155/2021/6678142.

    12. Song Y, Ye W, Ye H, Xie T, Shen W, Zhou L. Serum testosterone acts as a prognostic indicator in polycystic ovary syndrome- associated kidney injury. Physiol Rep. 2019;7(16):e14219. doi: 10.14814/phy2.14219.

    13. Xu Z, Huo J, Ding X, Yang M, Li L, Dai J, et al. Coenzyme Q10 improves lipid metabolism and ameliorates obesity by regulating CaMKII-mediated PDE4 inhibition. Sci Rep. 2017;7(1):8253. doi: 10.1038/s41598-017-08899-7.

    14. Lamia SS, Emran T, Rikta JK, Chowdhury NI, Sarker M, Jain P, et al. Coenzyme Q10 and silymarin reduce CCl4-induced oxidative stress and liver and kidney injury in ovariectomized rats-implications for protective therapy in chronic liver and kidney diseases. Pathophysiology. 2021;28(1):50-63. doi:10.3390/pathophysiology28010005.

    17. Izadi A, Ebrahimi S, Shirazi S, Taghizadeh S, Parizad M, Farzadi L, et al. Hormonal and metabolic effects of coenzyme Q10 and/or vitamin E in patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2019;104(2):319-27. doi: 10.1210/jc.2018-01221.

    18. Karamali M, Gholizadeh M. The effects of coenzyme Q10 supplementation on metabolic profiles and parameters of mental health in women with polycystic ovary syndrome. Gynecol Endocrinol. 2022;38(1):45-9. doi: 10.1080/09513590.2021.1991910.

    19. El Refaeey A, Selem A, Badawy A. Combined coenzyme Q10 and clomiphene citrate for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome. Reprod Biomed Online. 2014;29(1):119-24. doi: 10.1016/j. rbmo.2014.03.011.

    20. Shokrpour M, Hakimi F, Najdi N, Kamali A. Effects of coenzyme Q10 supplementation on anti-Müllerian hormone levels in patients with polycystic ovarian syndrome. Ann Med Health Sci Res. 2019;9:440-2.

    21. Zhang P, Yang C, Guo H, Wang J, Lin S, Li H, et al. Treatment of coenzyme Q10 for 24 weeks improves lipid and glycemic profile in dyslipidemic individuals. J Clin Lipidol. 2018;12(2):417-27.e5. doi: 10.1016/j.jacl.2017.12.006.

    22. Taghizadeh S, Izadi A, Shirazi S, Parizad M, Pourghassem Gargari B. The effect of coenzyme Q10 supplementation on inflammatory and endothelial dysfunction markers in overweight/obese polycystic ovary syndrome patients. Gynecol Endocrinol. 2021;37(1):26-30. doi: 10.1080/09513590.2020.1779689.

    23. Zhang T, He Q, Xiu H, Zhang Z, Liu Y, Chen Z, et al. Efficacy and safety of coenzyme Q10 supplementation in the treatment of polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Sci. 2023;30(4):1033-48. doi: 10.1007/s43032-022-01038-2.

    24. Mohammadi M, Fatemi I, Taghipour Z, Azin M, Kaeidi A, Hakimizadeh E, et al. Polycystic ovary syndrome can lead to neurocognitive changes in female rats treated with letrozole. Arch Neurosci. 2021;8(2):e112023. doi: 10.5812/ ans.112023.

    25. 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(7):830-9. doi: 10.1016/j. arcmed.2006.04.006.

    26. Fatemi I, Pak-Hashemi M, Mohammadi-Nasab M, Kaeidi A, Hakimizadeh E, Hassanipour M. The effects of endurance training in anxiety-like behaviors in rats with polycystic ovarian syndrome. J Jiroft Univ Med Sci. 2021;7(4):498-505. [Persian].

    27. Mohammadi-Nasab M, Fatemi I, Pak-Hashemi M, Abbasi- Fard M, Hassanipour M. The effects of Pistacia vera seed oil on anxiety and depressive-like behaviors in rats with polycystic ovary syndrome. Pistachio and Health Journal. 2019;2(1):1-9. doi: 10.22123/phj.2019.170505.1025.

    28. Jameie SB, Kazemian A, Sanadgol Z, Asadzadeh Bayqara S, Jameie MS, Farhadi M. Coenzyme Q10 reduces expression of apoptotic markers in adult rat nucleus accumbens dopaminergic neurons treated with methamphetamine. Mol Biol Rep. 2022;49(3):2273-81. doi: 10.1007/s11033-021- 07049-7.

    29. Fatemi I, Saeed Askari P, Hakimizadeh E, Kaeidi A, Esmaeil Moghaddam S, Pak-Hashemi M, et al. Chronic treatment with coenzyme Q10 mitigates the behavioral dysfunction of global cerebral ischemia/reperfusion injury in rats. Iran J Basic Med Sci. 2022;25(1):39-45. doi: 10.22038/ ijbms.2022.57630.12865.Modi K, Santani DD, Goyal RK, Bhatt PA. Effect of coenzyme Q10 on catalase activity and other antioxidant parameters in streptozotocin-induced diabetic rats. Biol Trace Elem Res. 2006;109(1):25-34. doi: 10.1385/bter:109:1:025.

    1. Hakimizadeh E, Hassanshahi J, Kaeidi A, Nematollahi MH, Taghipour Z, Rahmani M, et al. Ceftriaxone improves hepatorenal damages in mice subjected to D-galactose- induced aging. Life Sci. 2020;258:118119. doi: 10.1016/j. lfs.2020.118119.

    2. Iranmanesh F, Mousaei Amin A, Shamsizadeh A, Fatemi I, Malaki Rad A, Rahnama A. Effects of Pistacia vera hydro-alcoholic extract on carbon tetrachloride-induced hepatotoxicity in male rats. Iran J Pharmacol Ther. 2016;14(2):35-0.

    3. Mehrzadi S, Fatemi I, Esmaeilizadeh M, Ghaznavi H, Kalantar H, Goudarzi M. Hepatoprotective effect of berberine against methotrexate induced liver toxicity in rats. Biomed Pharmacother. 2018;97:233-9. doi: 10.1016/j. biopha.2017.10.113.

    4. Ahangarpour A, Oroojan AA, Khorsandi L, Kouchak M, Badavi M. Hypolipidemic and hepatoprotective effects of myricitrin and solid lipid nanoparticle-containing myricitrin on the male mouse model with type 2 diabetes induced by streptozotocin- nicotinamide. J Kerman Univ Med Sci. 2021;28(1):32-42. doi:10.22062/jkmu.2021.91562.

    5. Bazmandegan G, Amirteimoury M, Kaeidi A, Shamsizadeh A, Khademalhosseini M, Nematollahi MH, et al. Sumatriptan ameliorates renal injury induced by cisplatin in mice. Iran J Basic Med Sci. 2019;22(5):563-7. doi: 10.22038/ ijbms.2019.33620.8020.

    6. Taghizadeh Ghavamabadi R, Taghipour Z, Hassanipour M, Khademi M, Shariati M. Effect of maternal fluoxetine exposure on lung, heart, and kidney development in rat neonates. Iran J Basic Med Sci. 2018;21(4):417-21. doi: 10.22038/ ijbms.2018.27203.6650.

    7. Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. 2018;14(5):270-84. doi: 10.1038/nrendo.2018.24.

    8. Maliqueo M, Benrick A, Stener-Victorin E. Rodent models of polycystic ovary syndrome: phenotypic presentation,

    pathophysiology, and the effects of different interventions. Semin Reprod Med. 2014;32(3):183-93. doi: 10.1055/s- 0034-1371090.

    39. Al-Qadhi HI, Kadhim EJ, Ali RH. Coenzyme Q10 effects on body weight, serum testosterone level and oxidative stress in women with polycystic ovarian syndrome (PCOS). Int J Res Pharm Sci. 2017;8(3):378-83.

    40. Ye W, Xie T, Song Y, Zhou L. The role of androgen and its related signals in PCOS. J Cell Mol Med. 2021;25(4):1825-37. doi: 10.1111/jcmm.16205.

    41. Han Q, Wang J, Li W, Chen ZJ, Du Y. Androgen-induced gut dysbiosis disrupts glucolipid metabolism and endocrinal functions in polycystic ovary syndrome. Microbiome. 2021;9(1):101. doi: 10.1186/s40168-021-01046-5.

    42. Zhang J, Xing C, Zhao H, He B. The effectiveness of coenzyme Q10, vitamin E, inositols, and vitamin D in improving the endocrine and metabolic profiles in women with polycystic ovary syndrome: a network meta- analysis. Gynecol Endocrinol. 2021;37(12):1063-71. doi: 10.1080/09513590.2021.1926975.

    43. Falzarano C, Lofton T, Osei-Ntansah A, Oliver T, Southward T, Stewart S, et al. Nonalcoholic fatty liver disease in women and girls with polycystic ovary syndrome. J Clin Endocrinol Metab. 2022;107(1):258-72. doi: 10.1210/clinem/dgab658.

    44. Zumbro EL, Rao M, Balcom-Luker S, Broughton KS, LeMieux MJ. Whey protein supplementation improves the glycemic response and may reduce non-alcoholic fatty liver disease related biomarkers in women with polycystic ovary syndrome (PCOS). Nutrients. 2021;13(7):2451. doi: 10.3390/ nu13072451.

    45. Alqarni F, Eweis HS, Ali A, Alrafiah A, Alsieni M, Karim S, et al. The effect of coenzyme Q10 on liver injury induced by valproic acid and its antiepileptic activity in rats. Biomedicines. 2022;10(1):168. doi: 10.3390/biomedicines10010168.

    46. Fatima S, Suhail N, Alrashed M, Wasi S, Aljaser FS, AlSubki RA, et al. Epigallocatechin gallate and coenzyme Q10 attenuate cisplatin-induced hepatotoxicity in rats via targeting mitochondrial stress and apoptosis. J Biochem Mol Toxicol. 2021;35(4):e22701. doi: 10.1002/jbt.22701.