Primer Dismenore Patogenezinde İskemi ve Oksidatif Stresin Rolü

Year 2017, Volume: 7 Issue: 4, 205 - 210, 04.01.2018

Harika Shundo İrem Karaca Leyla Sevinç Fatma Behice Serinkan Cinemre , Birsen Aydemir Nermin Akdemir , Zübeyde Kaçal , Hakan Cinemre

https://doi.org/10.31832/smj.363216

Abstract

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.

Keywords

Primer dismenore, iskemi-modifiye albumin, malondialdehit

Role of Ischemia and Oxidative Stress in Primary Dysmenorrhea Pathogenesis

Abstract

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

References

• 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