Relationship between Serum Levels of Oxidative Stress Markers and Metabolic Syndrome Components in PCOS Women
Keywords:Antioxidants, Metabolic Syndrome, Oxidative Stress, PCOS
Background: Polycystic Ovarian Syndrome (PCOS) is a common endocrinological problem that leads to infertility in reproductive age. It is strongly associated with oxidative stress, which increases the risk of Metabolic Syndrome (Met-S) in women. This study aimed to evaluate the relationship between oxidative stress markers and metabolic syndrome parameters in PCOS women. Methods: In this cross-sectional study, we included age-matched 100 control and 150 PCOS (according to Rotterdam criteria). Anthropometric measurements were obtained from each subject. Lipid profile, Fasting Plasma Glucose (FPG), and insulin were determined. Serum Malondialdehyde (MDA), Nitric Oxide (NO), and Reactive Oxygen Species (ROS) levels are pro-oxidant indicators, while for antioxidant activities, Superoxide Dismutase (SOD), Catalase (CAT), Glutathione (GSH), Vitamin-C (Vit C), and Total Antioxidant Capacity (TAC) activity were measured by spectrophotometry. Results: In the PCOS group the SOD, CAT, GSH, Vit C, and TAC activity were significantly low, whereas NO, ROS, and MDA were significantly high (p < 0.05). In the PCOS group, the pro-oxidant MDA showed a negative correlation with HDL and a positive correlation with DBP. The antioxidants SOD and CAT showed a negative correlation with fasting blood glucose and triglycerides. Conclusion: The metabolic syndrome components of PCOS can induce oxidative stress, which is evidenced by a decrease in antioxidant defence mechanisms. It is probably because oxidative stress itself is the consequence of PCOS, more so with Met-S which increases the pro-oxidant state and decreases the anti-oxidant capacity in women.
Lizneva D, Suturina L, Walker W, et al. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril. 2016; 106:6-15. https://doi.org/10.1016/j. fertnstert.2016.05.003 PMid:27233760
Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet. 2007; 370(9588):685-97. https://doi.org/10.1016/S0140-6736(07)61345-2 PMid: 17720020
Deeks AA, Gibson-Helm ME, Teede HJ. Anxiety and depression in polycystic ovary syndrome: A comprehensive investigation. Fertil Steril. 2010; 93:2421-3. https://doi.org/10.1016/j.fertnstert.2009.09.018 PMid:20117778
Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: A systematic review and meta-analysis. Hum Reprod Update. 2010; 16:347-63. https://doi.org/10.1093/humupd/dmq001 PMid:20159883
Chen L, Xu WM, Zhang D. Association of abdominal obesity, insulin resistance, and oxidative stress in adipose tissue in women with Polycystic Ovary Syndrome. Fertil Steril. 2014; 102(4):1167-74. https://doi.org/10.1016/j. fertnstert.2014.06.027 PMid:25064406
Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005; 112:2735-52. https://doi.org/10.1161/ CIRCULATIONAHA. 105.169404 PMid:16157765
Caserta D, Adducchio G, Picchia S, et al. Metabolic syndrome and polycystic ovary syndrome: an intriguing overlapping. Gynecol Endocrinol. 2014; 30:397-402. https://doi.org/10.3109/09513590.2014.887673 PMid: 24552422
Lim SS, Kakoly NS, Tan JWJ, et al. Metabolic syndrome in polycystic ovary syndrome: A systematic review, meta-analysis and meta-regression. Obes Rev. 2019; 20(2):339-52. https://doi.org/10.1111/obr.12762 PMid:30339316
Otaghi M, Azami M, Khorshidi A, et al. The association between metabolic syndrome and polycystic ovary syndrome: A systematic review and meta-analysis. Diab Metab Syndr. 2019; 13(2):1481-9. https://doi. org/10.1016/j.dsx.2019.01.002 PMid:31336510
Agarwal A, Aponte-Mellado A, Premkumar BJ, et al. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol. 2012; 10:49. https://doi. org/10.1186/1477-7827-10-49 PMid:22748101 PMCid: PMC3527168
Murri M, Luque-Ramírez M, Insenser M, et al. Circulating markers of oxidative stress and Polycystic Ovary Syndrome (PCOS): A systematic review and meta-analysis. Hum Reprod Update. 2013; 19(3):268-88. https:// doi.org/10.1093/humupd/dms059 PMid:23303572
Desai V, Prasad NR, Manohar SM, et al. Oxidative stress in non-obese women with polycystic ovarian syndrome. J Clin Diagn Res. 2014; 8:CC01-03.
Gonzalez F, Rote NS, Minium J, Kirwan JP. Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. J Clin Endocrinol Metab. 2006; 91:336-40. https://doi.org/10.1210/jc.2005-1696 PMid:16249279
Papalou O, Victor VM, Diamanti-Kandarakis E. Oxidative stress in polycystic ovary syndrome. Curr Pharm Des. 2016; 22:2709-22. https://doi.org/10.2174/1 381612822666160216151852 PMid:26881435
Victor VM, Rocha M, Bañuls C, et al. Mitochondrial complex I impairment in leukocytes from polycystic ovary syndrome patients with insulin resistance. J Clin Endocrinol Metab. 2009; 94:3505-12. https://doi. org/10.1210/jc.2009-0466 PMid:19567514
The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004; 81:19- 25. https://doi.org/10.1016/j.fertnstert.2003.10.004
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972; 18:499-502. https://doi.org/10.1093/ clinchem/18.6.499 PMid:4337382
Cleeman JI, Grundy SM, Becker D, et al. Cholesterol Educ program, executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 2001; 285:2486-97. https://doi.org/10.1001/ jama.285.19.2486 PMid:11368702
Bernheim F, Bernheim MLC, Wilbur KM. The reaction between thiobarbituric acid and the oxidation products of certain lipids. J Biol Chem. 1948; 174(1):257-64. https://doi.org/10.1016/S0021-9258(18)57394-4 PMid: 18914082
Black MJ, Brandt RB. Spectrofluorometric analysis of hydrogen peroxide. Anal Biochem. 1974; 58(1):246-54 https://doi.org/10.1016/0003-2697(74)90464-3 PMid: 4825377
Grisham MB, Johnson GG, Lancaster JR. Quantitation of nitrate and nitrite in extracellular fluids. Methods Enzymol. 1996; 268:237-46, https://doi.org/10.1016/ S0076-6879(96)68026-4 PMid:8782590
Kazari D. A modified spectrophotometric assay of superoxide dismutase using nitrate formation by superoxide radical. Ind J Biochem Biophys. 2000; 57:201-4.
Aebi H. Catalase in vitro methods. Enzymology 1984; 105:121-6. https://doi.org/10.1016/S0076-6879(84)05016-3 PMid: 6727660
Moron M, Depierre J, Mannervik B. Levels of glutathione, glutathione reductase and glutathione s-transferase activities in rat lung and liver. Biochim Biophys Acta (BBA)- General Subjects. 1979; 582(1):67-78 https://doi. org/10.1016/0304-4165(79)90289-7
Subash-Babu P, Alshatwi AA, Ignacimuthu S. Beneficial antioxidative and antiperoxidative effect of cinnamaldehyde protect streptozotocin induced pancreatic β-cells damage in Wistar rats. Biomol Therapeut. (Seoul). 2014; 22(1):47-54. https://doi.org/10.4062/biomolther.2013.100 PMid: 24596621 PMCid:PMC3936432
Prieto P, Pineda M, Aguilar M. Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: Specific application to the determination of vitamin E. Anal Biochem. 1999; 269(2):337-41. https://doi.org/10.1006/abio.1999.4019 PMid:10222007
Rocha MP, Marcondes JAM, Barcellos CRG, et al. Dyslipidemia in women with polycystic ovary syndrome: incidence, pattern and predictors. Gynecol Endocrinol. 2011; 27:814-19. https://doi.org/10.3109/09513590.2010. 508852 PMid:20807166
Ruan X, Li M, Mueck AO. Why does Polycystic Ovary Syndrome (PCOS) need long-term management? Curr Pharm Des. 2018; 24:4685-92. https://doi.org/10.2174/1381612825666190130104922 PMid:30706800
Mujica LS, Bridi A, Méa RD, et al. Oxidative stress and metabolic markers in pre- and postnatal polycystic ovary syndrome rat protocols. J Infamm Res. 2018; 11:193-202. https://doi.org/10.2147/JIR.S160264 PMid:29805266 PMCid:PMC5960249
Abuja PM, Albertini R. Methods for monitoring oxidative stress, lipid peroxidation and oxidation resistance of lipoproteins. Clin Chim Acta. 2001; 306(1-2):1-17. https://doi.org/10.1016/S0009-8981(01)00393-X PMid: 11282089
Wang H, Ruan X, Li Y, et al. Oxidative stress indicators in Chinese women with PCOS and correlation with features of metabolic syndrome and dependency on lipid patterns. Arch Gynecol Obstet. 2019; 300(5):1413-21. https://doi.org/10.1007/s00404-019- 05305-7 PMid: 31549221
Zhang D, Luo WY, Liao H, et al. The effects of oxidative stress to PCOS. J Sichuan Univ Med Sci Ed. 2008; 39:421-3.
Kuşçu NK, Var A. Oxidative stress but not endothelial dysfunction exists in non-obese, young group of patients with polycystic ovary syndrome. Acta Obstet Gynecol Scand. 2009; 88:612-7. https://doi. org/10.1080/00016340902859315 PMid:19308750
Oyebanji O, Asaolu, M. Assessment of antioxidant status of women with polycystic ovarian syndrome. Asian Pac J Reprod. 2020; 9(1):9. https://doi.org/10.4103/2305- 0500.275523
Taylor BS, Kim YM, Wang Q, et al. Nitric oxide downregulates hepatocyte-inducible nitric oxide synthase gene expression. Arch Surg. 1997; 132:1177-83. https:// doi.org/10.1001/archsurg.1997.01430350027005 PMid:9366709
Zeng G, Quon MJ. Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells. J Clin Investig. 1996; 98:894-8. https://doi.org/10.1172/JCI118871 PMid: 8770859 PMCid:PMC507502
Nacul AP, Andrade CD, Schwarz P, et al. Nitric oxide and fibrinogen in polycystic ovary syndrome: Associations with insulin resistance and obesity. Eur J Obstet Gynecol Reprod Biol. 2007; 133:191-6. https://doi.org/10.1016/j. ejogrb.2006.09.009 PMid:17049715
Baskol G, Aygen E, Erdem F, et al. Assessment of paraoxonase 1, xanthine oxidase and glutathione peroxidase activities, nitric oxide and thiol levels in women with polycystic ovary syndrome. Acta Obstet Gynecol Scand. 2012; 91:326-30. https://doi.org/10.1111/j.1600- 0412.2011.01337.x PMid:22168506
Fatima Q, Amin S, Kawa IA, et al. Evaluation of antioxidant defense markers in relation to hormonal and insulin parameters in women with polycystic ovary syndrome (PCOS): A case-control study. Diabetes Metab Syndr. 2019; 13(3);1957-61. https://doi.org/10.1016/j. dsx.2019.04.032 PMid:31235121
Al-Azzawie HF, Humadi EH. Oxidative stress and antioxidant mechanisms in a sample of Iraqi patients with polycystic ovary syndrome. Iraqi J Comm Med. 2010; 3:196-200.
Kandasamy S, Sivagamasundari RI, Bupathy A, et al. Evaluation of insulin resistance and oxidative stress in obese patients with polycystic ovary syndrome. Int Jappl Biol Pharm. 2010; 2:391-98.
Seleem AK, El Refaeey AA, Shaalan D, et al. Superoxide dismutase in polycystic ovary syndrome patients undergoing intracytoplasmic sperm injection. J Assist Reprod Genet. 2014; 31:499-504. https://doi.org/10.1007/s10815- 014-0190-7 PMid:24526356 PMCid: PMC3969459
Sies H. Glutathione and its role in cellular functions. Free Radic Biol Med. 1999; 27:916-21. https://doi. org/10.1016/S0891-5849(99)00177-X PMid:10569624
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. 2001; 34(5):407-13. https://doi.org/10.1016/S0009- 9120(01)00245-4 PMid:11522279
Dincer Y, Akcay T, Erdem T, et al. DNA damage, DNA susceptibility to oxidation and glutathione level in women with polycystic ovary syndrome. Scand J Clin Lab Invest. 2005; 65(8):721-28. https://doi. org/10.1080/00365510500375263 PMid:16509054
Surapaneni KM, Vishnu PV. Lipid peroxidation, glutathion, ascorbic acid, vit E, antioxidant enzyme and serum homocysteine status in patients with polycystic ovary syndrome. Biol Med. 2009; 1(3):44-9.
Polak G, Kozioł-Montewka M, Gogacz M, et al. Total antioxidant status in peritoneal fluid in infertile women. Eur J Obstet Gynecol Reprod Biol. 2001; 94:261-63. https://doi.org/10.1016/S0301-2115(00)00352-3 PMid: 11165736
Moti M, Amini L, MirhoseiniArdakani SS, et al. Oxidative stress and antioxidant defense system in Iranian women with polycystic ovary syndrome. Iran J Reprod Med. 2015; 13:373-78.
Morelli NR, Scavuzzi BM, Miglioranza LHDS, et al. Metabolic syndrome components are associated with oxidative stress in overweight and obese patients. Arch Endocrinol Metab. 2018; 62:309-18. https://doi.org/10.20945/2359-3997000000036 PMid:29791650