Harika SHUNDO, İrem KARACA, Leyla SEVİNÇ, Fatma Behice SERİNKAN CİNEMRE, Birsen AYDEMİR, Nermin AKDEMİR, Zübeyde KAÇAL, Hakan CİNEMRE

Primer Dismenore Patogenezinde İskemi ve Oksidatif Stresin Rolü

Amaç: Primer dismenore, menstrual dönemde patolojik nedenlere bağlı olmayan ve prostaglandin sentezi tarafından uyarılabilen pelvik ağrıdır. Son çalışmalarda, primer dismenore ile iskemi/hipoksi arasındaki ilişki göstermiştir. İskemi Modifiye Albumin (IMA) iskeminin erken döneminin saptanmasında kullanılan yeni bir belirteçtir. Bu çalışmada iskemi ve oksidatif, stresin primer dismenore etiyopatogenezindeki rolünü ve semptomatolojisinin şiddeti ile ilişkisini araştırmayı planladık.Gereç ve Yöntem: Bu çalışmaya primer dismenoreli 47 üniversite öğrencisi dahil edildi. Her öğrencinin tam bir fizik ve jinekolojik muayenesi yapıldı. Ağrı şiddetini ölçmek için Görsel Analog Skala (VAS) kullanıldı (ağrı yok- 0, hayal edilebilen en şiddetli ağrı-10). Görsel Analog Skala ile, 1-4 arası skorlar hafif; 5-7 arası orta; ve 8-10 arası şiddetli ağrı olarak kabul edildi. Kan örnekleri, menstrüel döneminin üçüncü günü toplandı. Serum ayrıldıktan sonra analiz edilinceye kadar -80 °C'de saklandı. Serum IMA düzeyleri albumin kobalt bağlama (CAB) testi ile ölçüldü. Sonuçlar, serum albümin değerleri kullanılarak düzeltilmiş IMA (C-IMA) olarak ifade edildi. Malondialdehit (MDA) düzeyleri tiyobarbitürik asit reaktif madde (TBARS) kullanılarak ölçüldü ve sonuçlar μmol/L olarak verildi.Bulgular: C-IMA değerleri: hafif ağrılı grupta 0.867 ± 0.23; orta ağrılı grupta 1.279 ± 0.31 ve şiddetli ağrılu grupta 1.222 ± 0.20 bulundu. Oneway ANOVA ile karşılaştırıldığında, grupların ortalamaları arasında anlamlı fark vardı (p <0.024). Tukey testi kullanılarak hafif ağrılı gruptaki C-IMA değerlerinin orta ağrılı olan grubun C-IMA değerlerinden anlamlı derecede düşük olduğu görüldü (p = 0,021). MDA sonuçları: hafif ağrılı grupta 9.01 ± 0.64; orta ağrılı grupta15.20 ± 6.86 ve şiddetli ağrılı grupta 11.78 ± 1.97 bulundu. Oneway-ANOVA ile gruplar arasında istatistiksel anlamlı fark vardı (p <0.016). Tukey testi ile grup karşılaştırmaları, hafif dismenoreli grup ile şiddetli ağrılı grup arasında anlamlı fark olduğunu gösterdi (p <0.016). Sonuçlar: Primer dismenore hastalarında C-IMA ve MDA düzeyleri artmaktadır. Ayrıca, bunların seviyeleri, ağrının şiddeti ile de ilişkiliydi. Bu bulgular, primer dismenorede iskemi ve oksidatif stresin rol oynadığını düşündürmektedir. Muhtemelen ağrı oluşturan mekanizmalar, aynı zamanda oksidatif stres ve iskemiye de neden olmaktadır. İskemi ve ağrı ile birlikte oksidatif stres oluşturan bu mekanizmalar daha ileri araştırmalar ile aydınlatılmalıdır.

Anahtar Kelimeler:

Primer dismenore, iskemi-modifiye albumin, malondialdehit

Role of Ischemia and Oxidative Stress in Primary Dysmenorrhea Pathogenesis

Objective: Primary dysmenorrhea is pelvic pain without pathologic reasons during the menstrual period, induced by prostaglandin synthesis. Last studies have shown the relation of primary dysmenorrhea with ischemia/hypoxia. Ischemia-Modified Albumin (IMA) is a marker used for detecting the early period of ischemia. In this study we planned to investigate role of ischemia and oxidative stress in etiopathogenesis of primary dysmenorrhea according to the severity of its symptomatology.Materials and Methods: 47 female university students with primary dysmenorrhea were included in this study. Each student passed through the full physical and gynecological examination. Visual Analog scale (VAS) was used to measure pain intensity (no pain-score of 0;worst imaginable pain-score of 10). VAS grading from 1-4 was accepted as mild; 5-7 as moderate; and 8-10 as severe pain. Blood samples were collected from all participants on the third day of mens period. After separation of serum, they were kept at -80°C until analyzed. Serum IMA levels were measured by albumin cobalt binding (CAB) test. The results were corrected by using serum albumin values-expressed as corrected IMA(C-IMA). Malondialdehyde (MDA) levels were measured by using thiobarbituric acid reactive substance (TBARS) and the results were expressed as µmol/L.Results: C-IMA values were: 0.867±0.23 in mild; 1.279±0.31 in moderate and 1.222±0.20 in severe pain group. There were significant difference between the averages of groups with Oneway ANOVA (p<0.024). By using Tukey test the C-IMA values in group with mild pain found significantly lower than the C-IMA values of the group with moderate pain(p = 0,021). MDA results were: 9.01±0.64 in the mild; 11.78±1.97 in the moderate and 15.20± 6.86 severe pain group. The difference between groups with Oneway-ANOVA was statistically significant (p<0.016). Group comparisons with Tukey test showed significant difference between the group with mild dysmenorrhea and the group with severe pain (p<0.016). Conclusions: C-IMA and MDA levels increased in patients with primary dysmenorrhea. Their levels were related with the severity of the pain, suggesting roles of ischemia and oxidative stress in primary dysmenorrhea. Probably pain-generating mechanisms also produce oxidative stress and ischemia. Molecular mechanisms which induce oxidative stress together with ischemia and pain should be investigated in further studies.

Keywords:

Primary dysmenorrhea, ischemia-modified albumin, malondialdehyde,

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Referans1. Oladosu FA, Tu FF, Hellman KM. Nonsteroidal antiinflammatory drug resistance in dysmenorrhea: epidemiology, causes, and treatment. Am J Obstet Gynecol. 2017pii: S0002-9378(17)31095-5. PMID: 28888592
Referans2. Dawood MY. Primary dysmenorrhea: advances in pathogenesis and management. Obstet Gynecol. 2006;108(2):428-41. PMID: 16880317
Referans3. Iacovides S, Avidon I, Baker FC. What we know about primary dysmenorrhea today: a critical review. Hum Reprod Update. 2015;21(6):762-78. PMID: 26346058
Referans4. Akerlund M. Involvement of oxytocin and vasopressin in the pathophysiology of preterm labor and primary dysmenorrhea. Prog Brain Res. 2002;139:359-65. PMID: 12436949
Referans5. Valtonen P, Punnonen K, Saarelainen H, Heiskanen N, Raitakari OT, Juonala M, et al. ADMA concentration changes across the menstrual cycle and during oral contraceptive use: the cardiovascular risk in Young Finns Study. Eur J Endocrinol. 2010;162(2):259-65. PMID: 19934267
Referans6. Akdemir N, Cinemre FB, Bostancı MS, Cinemre H, Ünal O, Ozden S, Cevrioglu AS, Kacal Z, Akdemir R The correlation of serum asymmetric dimethylarginine and anti-Müllerian hormone in primary dysmenorrhea. Kaohsiung J Med Sci. 2016;32(8):414-9. PMID: 27523455
Referans7. Turhan N, Çelik H, Duvan Cİ, Onaran Y, Aydın M, Armutcu F. Investigation of oxidative balance in patients with dysmenorrhea by multiple serum markers. J Turk Ger Gynecol Assoc. 2012;13(4):233-6. PMID: 24592048
Referans8. Ma H, Hong M, Duan J, Liu P, Fan X, Shang E, Su S, Guo J, Qian D, Tang Y. Altered cytokine gene expression in peripheral blood monocytes across the menstrual cycle in primary dysmenorrhea: A case-control study. PLoS One. 2013;8(2):e55200. PMID: 23390521
Referans9. Dikensoy E, Balat O, Pençe S, Balat A, Cekmen M, Yurekli MJ. Malondialdehyde, nitric oxide and adrenomedullin levels in patients with primary dysmenorrhea. Obstet Gynecol Res. 2008;34(6):1049-53. PMID: 19012707
Referans10. Aksoy AN, Laloglu E, Ozkaya AL, Yilmaz EP. Serum heme oxygenase-1 levels in patients with primary dysmenorrhea. Arch Gynecol Obstet. 2017;295(4):929-934. PMID: 28236018
Referans11. Frijhoff J, Winyard PG, Zarkovic N, Davies SS, Stocker R, Cheng D, Knight AR, Taylor EL, Oettrich J, Ruskovska T, Gasparovic AC, Cuadrado A, Weber D, Poulsen HE, Grune T, Schmidt HH, Ghezzi P. Clinical relevance of biomarkers of oxidative stress. Antioxid Redox Signal. 2015;23(14):1144-70. PMID: 26415143.
Referans12. Evans J, Salamonsen LA. Inflammation, leukocytes and menstruation. Rev Endocr Metab Disord. 2012;13(4):277-88. PMID: 22865231.
Referans13. Apple FS, Wu AH, Mair J, Ravkilde J, Panteghini M, Tate J, Pagani F, Christenson RH, Mockel M, Danne O, Jaffe AS; Committee on Standardization of Markers of Cardiac Damage of the IFCC. Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome. Clin Chem. 2005;51(5):810-24. PMID: 15774573
Referans14. Dominguez-Rodriguez A, Abreu-Gonzalez P. Current role of ischemia-modified albumin in routine clinical practice. Biomarkers. 2010;15(8):655-62. PMID: 20874662
Referans15. Lee E, Eom JE, Jeon KH, Kim TH, Kim E, Jhon GJ, Kwon Y. Evaluation of albumin structural modifications through cobalt-albumin binding (CAB) assay. J Pharm Biomed Anal. 2014;91:17-23. PMID: 2443427
Referans16. Zurawska-Płaksej E, Grzebyk E, Marciniak D, Szymańska-Chabowska A, Piwowar A. Oxidatively modified forms of albumin in patients with risk factors of metabolic syndrome. J Endocrinol Invest. 2014;37(9):819-27. PMID: 24957167
Referans17. Lippi G, Montagnana M, Salvagno GL, Guidi GC. Standardization of ischemia-modified albumin testing: adjustment for serum albumin. Clin Chem Lab Med. 2007;45(2):261-62. PMID: 17311519
Referans18. Sbarouni E, Georgiadou P, Voudris V. Ischemia modified albumin changes- review and clinical implications. Clin Chem Lab Med 2011;49:177-84. PMID: 21083441
Referans19. D'souza JM, Pai VR, Harish S, Shriyan C, D'souza N. IMA and IMAR in serum and saliva of preeclampsia--a preliminary study. Hypertens Pregnancy. 2014;33(4):440-8. PMID: 25019475
Referans20. Ellidag HY, Bulbuller N, Eren E, Abusoglu S, Akgol E, Cetiner M et al. Ischemia-modified albumin: could it be a new oxidative stress biomarker for colorectal carcinoma? Gut Liver. 2013;7(6):675-80. PMID: 24312708
Referans21. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302-10. PMID: 672633
Referans22. Bar-Or D, Curtis G, Rao N, Bampos N, Lau E. Characterization of the Co2+ and Ni2+ binding amino-acid residues of the N-terminus of human albümin. An insight into the mechanism of a new assay for myocardial ischemia. Eur J Biochem. 2001;268(1):42-7. PMID: 11121100
Referans23. Yeh ML, Chen HH, So EC, Liu CF. A study of serum malondialdehyde and interleukin- 6 levels in young women with dysmenorrhea in Taiwan. Life Sci 2004; 75: 669–673. PMID: 15172176
Referans24. Seshadri Reddy V, Duggina P, Vedhantam M, Manne M, Varma N, Nagaram S.J Maternal serum and fetal cord-blood ischemia-modified albumin concentrations in normal pregnancy and preeclampsia: a systematic review and meta-analysis. Matern Fetal Neonatal Med. 2017; 29:1-12. PMID: 28817994
Referans25. Nazik S, Avci V, Küskü Kiraz Z. Ischemia-modified albumin and other inflammatory markers in the diagnosis of appendicitis in children. Ulus Travma Acil Cerrahi Derg. 2017;23(4):317-321. PMID: 28762455
Referans26. Yavuz F, Biyik M, Asil M, Dertli R, Demir A, Polat H, Uysal S, Ataseven H. Serum ischemia modified albumin (IMA) concentration and IMA/albumin ratio in patients with hepatitis B-related chronic liver diseases. Turk J Med Sci. 2017;12;47(3):947-953. PMID: 28618749
Referans27. Derikx JP, Schellekens DH, Acosta S. Serological markers for human intestinal ischemia: A systematic review. Best Pract Res Clin Gastroenterol. 2017;31(1):69-74. PMID: 28395790
Referans28. Terrin G, Stronati L, Cucchiara S, De Curtis M.J. Serum Markers of Necrotizing Enterocolitis: A Systematic Review. Pediatr Gastroenterol Nutr. 2017 Apr 5. PMID: 28379923
Referans29. Koike H, Egawa H, Ohtsuka T, Yamaguchi M, Ikenoue T, Mori N. Correlation between dysmenorrheic severity and prostaglandin production in women with endometriosis. Prostaglandins Leukot Essent Fatty Acids 1992;46:133-7. PMID: 1502250
Referans30. Ye S, Zhou X, Lin J, Chen P. Asymmetric Dimethylarginine induced apoptosis and dysfunction of endothelial progenitor cells: Role of endoplasmic reticulum stress pathway. Biomed Res Int. 2017;2017:6395601. PMID: 28589144