Exp Clin Endocrinol Diabetes 2017; 125(08): 506-513
DOI: 10.1055/s-0043-111241
Article
© Georg Thieme Verlag KG Stuttgart · New York

Plasmatic and Intracellular Markers of Oxidative Stress in Normal Weight and Obese Patients with Polycystic Ovary Syndrome

Chantal Di Segni
1   Department of Internal Medicine, Operative Unit of Endocrinology, Catholic University of Sacred Heart, Largo A. Gemelli 8, Rome, Italy
,
Andrea Silvestrini
2   Institute of Biochemistry and Clinical Biochemistry, Catholic University of Sacred Heart, Largo F. Vito 1, Rome, Italy
,
Romana Fato
3   Deptartment Of Pharmacology and Biotechnology (FaBiT), University of Bologna, Via S. Donato 15, Bologna, Italy
,
Christian Bergamini
4   CIRI-HST, University of Bologna, Via Tolara di Sopra, Ozzano dell'Emilia, Italy
,
Francesco Guidi
5   Department Of Obstetrics and Gynecology, Catholic University of Sacred Heart, Largo A. Gemelli 8, Rome, Italy
,
Sebastiano Raimondo
1   Department of Internal Medicine, Operative Unit of Endocrinology, Catholic University of Sacred Heart, Largo A. Gemelli 8, Rome, Italy
,
Elisabetta Meucci
2   Institute of Biochemistry and Clinical Biochemistry, Catholic University of Sacred Heart, Largo F. Vito 1, Rome, Italy
,
Daniela Romualdi
5   Department Of Obstetrics and Gynecology, Catholic University of Sacred Heart, Largo A. Gemelli 8, Rome, Italy
,
Rosanna Apa
5   Department Of Obstetrics and Gynecology, Catholic University of Sacred Heart, Largo A. Gemelli 8, Rome, Italy
,
Antonio Lanzone
5   Department Of Obstetrics and Gynecology, Catholic University of Sacred Heart, Largo A. Gemelli 8, Rome, Italy
,
Antonio Mancini
1   Department of Internal Medicine, Operative Unit of Endocrinology, Catholic University of Sacred Heart, Largo A. Gemelli 8, Rome, Italy
› Author Affiliations
Further Information

Publication History

received 30 January 2017
first decision 06 May 2017

accepted 11 May 2017

Publication Date:
04 July 2017 (online)

Abstract

Introduction Insulin resistance (IR) is associated with polycystic ovary syndrome (PCOS). Oxidative stress (OS) is, in turn, related to IR. Studies in PCOS evidenced an increase in OS markers, but they are mainly performed in obese patients, while the complex picture of normal weight PCOS is still poorly investigated.

Matherials and Methods To investigate OS in PCOS and relationship with hormonal and metabolic picture, we performed a case-control study in 2 PCOS groups: normal weight (N-PCOS, n=21, age 18–25 ys, mean±SEM BMI 20.7±0.2 kg/m2) and obese (OB-PCOS, n=15, 20–30 ys, BMI 32.8±1.1), compared with control groups matched for BMI: normal (N-C, n=10, 20–30 ys, BMI 21.6±0.9) and obese (OB-C, n=20, 21–31ys, BMI 36.8±1.0). Malondialdehyde (MDA) in blood plasma and peripheral mononuclear cells, obtained by density-gradient centrifugation, was assayed spectrophotometrically by TBARS assay. CoenzymeQ10 (CoQ10) in plasma and cells was assayed by HPLC. Plasma Total Antioxidant Capacity (TAC) was also measured by spectrophotometric method.

Results PCOS patients exhibited higher Testosterone levels than controls, but OB-PCOS had highest HOMA (Homeostasis Model Assessment) index, suggesting marked insulin resistance. Despite plasma MDA levels were not significantly different (N-PCOS 3380±346.94 vs. N-C 7 120±541.66; OB-PCOS 5 517.5±853.9 vs. OB. 3 939.66±311.2 pmol/ml), intracellular MDA levels were significantly higher in N-PCOS than controls (mean 3 259±821.5 vs. 458±43.2 pmol/106/cells) and higher than OB-PCOS, although not significantly (1363.1±412.8 pmol/106/cells). Intracellular CoenzymeQ10 was higher in N-PCOS than in N-C, but the highest levels were found in OB-C.

Conclusions Our data, while confirming the presence of OS in obese PCOS patients in agreement with literature, suggest that OS could be present also in normal weight PCOS, but it can be revealed in tissue rather than in plasma. The relationship with metabolic status remains to be established, but could be a physiopathological basis for antioxidant treatment in such patients.

 
  • References

  • 1 Asunción M, Calvo RM, San Millán JL. et al. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab 2000; 85: 2434-2438
  • 2 Azziz R, Woods KS, Reyna R. et al. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 2004; 89: 2745-2749
  • 3 Carmina E, Lobo R. Polycystic Ovary Syndrome (PCOS): Arguably the most common endocrinopathy is associated with significant morbidity in women. J Clin Endocrinol Metab 1999; 84: 1897-1899
  • 4 Moran C, Tena G, Moran S. et al. Prevalence of polycystic ovary syndrome and related disorders in mexican women. Gynecol Obstet Invest 2010; 69: 274-280
  • 5 Sanchón R, Gambineri A, Alpañés M. et al. Prevalence of functional disorders of androgen excess in unselected premenopausal women: a study in blood donors. Hum Reprod 2012; 27: 1209-1216
  • 6 Escobar-Morreale HF, Luque-Ramírez M, San Millán JL. The molecular-genetic basis of functional hyperandrogenism and the polycystic ovary syndrome. Endocr Rev 2005; 26: 251-282
  • 7 Kalyanaraman B. Teaching the basics of redox biology to medical and graduate students: Oxidants, antioxidants and disease mechanisms. Redox Biol 2013; 1: 244-257
  • 8 Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. Free Radic Biol Med 1991; 449-450
  • 9 Turrens JF, Boveris A. Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem J 1980; 191: 421-427
  • 10 Babior BM, Kipnes RS, Curnutte JT. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest 1973; 52: 741-744
  • 11 Valko M, Leibfritz D, Moncol J. et al. ì, Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007; 39: 44-84
  • 12 Mancini A, Leone E, Festa R. et al. Evaluation of antioxidant systems (coenzyme Q10 and total antioxidant capacity) in morbid obesity before and after biliopancreatic diversion. Metabolism 2008; 57: 1384-1389
  • 13 Bayram F, Kocer D, Ozsan M. et al. Evaluation of endothelial dysfunction, lipid metabolism in women with polycystic ovary syndrome: relationship of paraoxonase 1 activity, malondialdehyde levels, low-density lipoprotein subfractions, and endothelial dysfunction. Gynecol Endocrinol 2012; 28: 497-501
  • 14 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: 268-288
  • 15 Vincent HK, Taylor AG. Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans. Int J Obes 2006; 30: 400-418
  • 16 Liu S, Navarro G, Mauvais-Jarvis F. Androgen excess produces systemic oxidative stress and predisposes to β-cell failure in female mice. PLoS One 2010; 5: e11302
  • 17 Katsikis I, Mouslech T, Kourtis A. et al. Oligo-ovulation or anovulation and hyperandrogenemia contribute to the decreased serum adiponectin levels in normal-weight women with PCOS with obesity and insulin resistance. Fertil Steril 2009; 91: e3
  • 18 Fauser BCJM. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19-25
  • 19 Matthews DR, Hosker JP, Rudenski AS. et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
  • 20 Rice-Evans C., Miller NJ. Total antioxidant Status in plasma and body fluids. Methods enzymol 1994; 234: 279-293
  • 21 Meucci E, Milardi D, Mordente A. et al. Total antioxidant capacity in patients with varicoceles. Fertil Steril 2003; 79: 1577-1583
  • 22 Takada M, Ikenoya S, Yuzuriha T. et al. Studies on reduced and oxidized coenzyme Q (ubiquinones). The determination of oxidation-reduction levels of coenzyme Q in mitochondria, microsomes and plasma by high-performance liquid chromatography. Biochim Biophys Acta 1982; 679: 308-314
  • 23 Berkban T, Boonprom P, Bunbupha S. et al. Ellagic Acid Prevents L-NAME-Induced Hypertension via Restoration of eNOS and p47phox Expression in Rats. Nutrients 2015; 7: 5265-5280
  • 24 Deepika MLN, Nalini S, Maruthi G. et al. Analysis of oxidative stress status through MN test and serum MDA levels in PCOS women. Pak J Biol Sci 2014; 17: 574-577
  • 25 Kaya C, Erkan AF, Cengiz SD. et al. Advanced oxidation protein products are increased in women with polycystic ovary syndrome: relationship with traditional and nontraditional cardiovascular risk factors in patients with polycystic ovary syndrome. Fertil Steril 2009; 92: 1372-1377
  • 26 Assumpção CR, Brunini TMC, Matsuura C. et al. Impact of the L-arginine-nitric oxide pathway and oxidative stress on the pathogenesis of the metabolic syndrome. Open Biochem J 2008; 2: 108-115
  • 27 Bonomini F, Rodella LF, Rezzani R. Metabolic Syndrome, Aging and Involvement of Oxidative Stress. Aging Dis 2015; 6: 109-120
  • 28 Ceriello A, Motz E.. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arter Thromb Vasc Biol 2004; 24: 816-823
  • 29 Li L, Li J. Link between oxidative stress and insulin resistance. Chin Med Sci J 2007; 22: 254-259
  • 30 De Caterina R, Cipollone F, Filardo FP. et al. Low-density lipoprotein level reduction by the 3-hydroxy-3-methylglutaryl coenzyme-A inhibitor simvastatin is accompanied by a related reduction of F2-isoprostane formation in hypercholesterolemic subjects: No further effect of vitamin E. Circulation 2002; 106: 2543-2549
  • 31 Evans JL, Goldfine ID, Maddux BA. et al. Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction?. Diabetes 2003; 52: 1-8
  • 32 Ciampelli M, Fulghesu AM, Cucinelli F. et al. Impact of insulin and body mass index on metabolic and endocrine variables in polycystic ovary syndrome. Metabolism 1999; 48: 167-172
  • 33 Littarru GP, Tiano L. Clinical aspects of coenzyme Q10: An update. Nutrition 2010; 26: 250-254
  • 34 Hargreaves IP. Ubiquinone: Cholesterol’s reclusive cousin. Ann Clin Biochem 2003; 40: 207-218
  • 35 Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr 2001; 20: 591-598
  • 36 Echtay KS, Winkler E, Klingenberg M. Coenzyme Q is an obligatory cofactor for uncoupling protein function. Nature 2000; 408: 609-613
  • 37 Strauss RS. Comparison of serum concentrations of alpha-tocopherol and beta-carotene in a cross-sectional sample of obese and nonobese children (NHANES III). National Health and Nutrition Examination Survey. J Pediatr 1999; 134: 160-165
  • 38 Menke T, Niklowitz P, de Sousa G. et al. Comparison of coenzyme Q10 plasma levels in obese and normal weight children. Clin Chim Acta 2004; 349: 121-127
  • 39 Miles MV, Morrison JA, Horn PS. et al. Coenzyme Q10 changes are associated with metabolic syndrome. Clin Chim Acta. 2004; 344: 173-179
  • 40 Lenaz G, Bovina C, D'Aurelio M. et al. Role of mitochondria in oxidative stress and aging. Ann N Y Acad Sci 2002; 959: 199-213
  • 41 Mancini A, Leone E, Festa R. et al. Evaluation of antioxidant systems (coenzyme Q10 and total antioxidant capacity) in morbid obesity before and after biliopancreatic diversion for morbid obesity: preliminary data. Metabolism 2008; 57: 1384-1389
  • 42 Melissas J, Malliaraki N, Papadakis JA. et al. Plasma antioxidant capacity in morbidly obese patients before and after weight loss. Obes Surg 2006; 16: 314-320
  • 43 Roberts CK, Vaziri ND, Barnard RJ. Effect of diet and exercise intervention on blood pressure, insulin, oxidative stress, and nitric oxide availability. Circulation 2002; 106: 2530-2532
  • 44 Niki E, Noguchi N. Evaluation of antioxidant capacity. What capacity is being measured by which method? IUBMB Life 2000; 50: 323-329
  • 45 Mancini A, Martorana GE, Magini M. et al. Oxidative stress and metabolic syndrome: Effects of a antioxidants enriched diet on insulin resistance. Clin Nutr. 1-16
  • 46 Insenser M, Montes-Nieto R, Murri M. et al. Proteomic and metabolomic approaches to the study of polycystic ovary syndrome. Mol Cell Endocrinol 2013; 370: 65-77
  • 47 Ma X, Fan L, Meng Y. et al. Proteomic analysis of human ovaries from normal and polycystic ovarian syndrome. Mol Hum Reprod 2007; 13: 527-535
  • 48 Misiti S, Stigliano A, Borro M. et al. Proteomic profiles in hyperandrogenic syndromes. J Endocrinol Invest 2010; 33: 156-164
  • 49 Corton M, Botella-Carretero JI, Lopez JA. et al. Proteomic analysis of human omental adipose tissue in the polycystic ovary syndrome using two-dimensional difference gel electrophoresis and mass spectrometry. Hum Reprod 2008; 23: 651-661
  • 50 Corton M, Botella-Carretero JI, Benguria A. et al. Differential gene expression profile in omental adipose tissue in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2007; 92: 328-337
  • 51 Aguirre GA, De Ita JR, de la Garza RG. et al. Insulin-like growth factor-1 deficiency and metabolic syndrome. J Transl Med 2016; 6: 14-3
  • 52 Mancini A, Festa R, Di Donna V. et al. Hormones and antioxidant systems: Role of pituitary and pituitary-dependent axes. J Endocrinol Invest 2010; 33: 422-433