Levels of oxidative stress and apoptosis-related biomarkers in endometriosis
Yıl 2023,
Cilt: 48 Sayı: 2, 480 - 488, 02.07.2023
Dilara Ülger Özbek
,
Savaş Karakuş
,
Sevtap Bakır
Öz
Purpose: In this study, the apoptosis marker M30, the oxidative stress markers malondialdehyde, (MDA) and asymmetric dimethyl arginine (ADMA) have been studied in the context of endometriosis.
Materials and Methods: This prospective case-control study comprises 31 patients diagnosed with endometriosis and 31 controls. ADMA and M30 levels in blood serum were measured by the enzyme-linked immunosorbent assay (ELISA) method, and MDA levels were measured by the spectrophotometric method. In addition, some biochemical parameters and cancer antigen-125 (CA-125) levels were also measured.
Results: M30 levels were statistically lower in endometriosis patients (271.5 IU/L) than in controls (371.3 IU/L). ADMA levels were higher in endometriosis patients (19.3 ng/L) compared to controls (12.7 ng/L). CA-125 levels were statistically higher in the endometriosis patients (65.1 U/mL) compared to the controls (19.0 U/mL). There was no significant difference between the two groups in MDA levels. The results regarding dyspareunia, pelvic pain, AST, and ALP were statistically significant.
Conclusion: In our study, decreased M30 levels in the patient group were associated with reduced apoptosis in endometriosis. ADMA levels, elevated with the increase of oxidative stress, were higher in the patients. MDA levels, an indicator of increased oxidative stress, were also higher in the patient group. This study constitutes the first data regarding endometriosis patients' ADMA, M30, and MDA levels.
Destekleyen Kurum
Sivas Cumhuriyet Üniversitesi Bilimsel Araştırma Projeleri
Teşekkür
The researchers thank Ziynet Çınar, Ph.D, for statistical analysis support. This study was supported as a Master Thesis by the Sivas Cumhuriyet University Scientific Research Projects (CÜBAP) project numbered T-606.
Kaynakça
- Kao LGL, Giudice L. Endometriosis. Lancet. 2004;364:1789-99.
- Stratton P, Winkel C, Premkumar A, Chow C, Wilson J, Hearns-Stokes R et al. Diagnostic accuracy of laparoscopy, magnetic resonance imaging, and histopathologic examination for the detection of endometriosis. Fertil Steril. 2003;79:1078-85.
- Brosens I, Puttemans P, Campo R, Gordts S, Brosens J. Non-invasive methods of diagnosis of endometriosis. Curr Opin Obstet Gynecol. 2003;15:519-22.
- Sampson JA. Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol. 1927;14:422-69.
- Chantalat E, Valera MC, Vaysse C, Noirrit E, Rusidze M, Weyl A et al. Estrogen receptors and endometriosis. Int J Mol Sci. 2020;21:2815.
- Patel BG, Rudnicki M, Yu J, Shu Y, Taylor RN. Progesterone resistance in endometriosis: origins, consequences and interventions. Acta Obstet Gynecol Scand. 2017;96:623-32.
- Yang WC, Chen HW, Au HK, Chang CW, Huang CT, Yen YH et al. Serum and endometrial markers. Best Pract Res Clin Obstet Gynaecol. 2004;18:305-18.
- Gonçalves G, Camargo-Kosugi C, Bonetti T, Invitti A, Girão M, Silva I et al. p27 kip1 overexpression regulates VEGF expression, cell proliferation and apoptosis in cell culture from eutopic endometrium of women with endometriosis. Apoptosis. 2015;20:327-35.
- Gaben AM, Saucier Cc, Bedin M, Redeuilh Gr, Mester J. Mitogenic activity of estrogens in human breast cancer cells does not rely on direct induction of mitogen-activated protein kinase/extracellularly regulated kinase or phosphatidylinositol 3-kinase. Mol Endocrinol. 2004;18:2700-13.
- Yilmaz BD, Bulun SE. Endometriosis and nuclear receptors. Hum Reprod Update. 2019;25:473-85.
- Sansone AM, Hisrich BV, Young RB, Abel WF, Bowens Z, Blair BB et al. Evaluation of BCL6 and SIRT1 as non-invasive diagnostic markers of endometriosis. Curr Issues Mol Biol. 2021;43:1350-60.
- Koruk I, Özdemır H, Aydinli M, Bekmen N, Tarakçioğlu M, Koruk M. The relation between serum cytokeratin 18 and acute pancreatitis: can it be a serological predictive marker? Turk J Gastroenterol. 2012;23:759-63.
- Demiray M, Ulukaya EE, Arslan M, Gokgoz S, Saraydaroglu O, Ercan I et al. Response to neoadjuvant chemotherapy in breast cancer could be predictable by measuring a novel serum apoptosis product, caspase-cleaved cytokeratin 18: a prospective pilot study. Cancer Invest. 2006;24:669-76.
- Ulukaya E, Yilmaztepe A, Akgoz S, Linder S, Karadag M. The levels of caspase-cleaved cytokeratin 18 are elevated in serum from patients with lung cancer and helpful to predict the survival. Lung cancer. 2007;56:399-404.
- Meresman GF, Bilotas MA, Lombardi E, Tesone M, Sueldo C, Baranao RI. Effect of GnRH analogues on apoptosis and release of interleukin-1beta and vascular endothelial growth factor in endometrial cell cultures from patients with endometriosis. Hum Reprod. 2003;18:1767-71.
- Taylor RN, Lebovic DI, Mueller MD. Angiogenic factors in endometriosis. Ann N Y Acad Sci. 2002;955:89-100.
- Gilligan DM, Quyyumi AA, Cannon 3rd R. Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women. Circulation. 1994;89:2545-51.
- Palmer RM, Ferrige A, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327:524-26.
- Vita JA, Keaney Jr JF. Endothelial function: a barometer for cardiovascular risk. Circulation. 2002:640-42.
- Xia W, Feng W, Guan M, Yu Y, Li J, Qu X. Increased levels of asymmetric dimethylarginine and C-reactive protein are associated with impaired vascular reactivity in essential hypertension. Clin Exp Hypertens. 2010;32:43-8.
- Sydow K, Münzel T. ADMA and oxidative stress. Atheroscler Suppl. 2003;4:41-51.
- Killic E, Yazar S, Saraymen R, Hozbilge H. Serum malondialdehyde level in patients infected with Ascaris lumbricodes. World J Gastroentrol. 2003;9:2332-34.
- Jain SK. Evidence for membrane lipid peroxidation during the in vivo aging of human erythrocytes. Biochim Biophys Acta Biomembr. 1988;937:205-10.
- Gludice L. Clinical practice endometriosis. N Engl J Med. 2010;362:2389-88.
- Avant RF. Dysmenorrhea. Prim Care. 1988;15:549-59.
- Nisenblat V, Bossuyt PM, Shaikh R, Farquhar C, Jordan V, Scheffers CS et al. Blood biomarkers for the non‐invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 1996;2016.
- Kashanian M, Sariri E, Vahdat M, Ahmari M, Moradi Y, Sheikhansari N. A comparison between serum levels of interleukin-6 and CA125 in patients with endometriosis and normal women. Med J Islam Repub Iran. 2015;29:280.
- Rocha ALL RF, Taylor RN. Angiogenesis and endometriosis. Gynecol Obstet Int. 2013:1-8.
- Vaskivuo T, Stenbäck F, Karhumaa P, Risteli J, Dunkel L, Tapanainen JS. Apoptosis and apoptosis-related proteins in human endometrium. Mol Cell Endocrinol. 2000;165:75-83.
- Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35:495-516.
- Büyükgebiz O, Caferler J. Apoptoz. Sendrom. 2001;13:102-7.
- Lee KS, Chung JY, Jung YJ, Chung WY, Park JH, Sheen SS et al. The significance of caspase-cleaved cytokeratin 18 in pleural effusion. Tuberc Respir Dis. 2014;76:15-22.
- Harada T, Iwabe T, Terakawa N. Role of cytokines in endometriosis. Fertil Steril. 2001;76:1-10.
- Augoulea A, Mastorakos G, Lambrinoudaki I, Christodoulakos G, Creatsas G. The role of the oxidative-stress in the endometriosis-related infertility. Gynecol Endocrinol. 2009;25:75-81.
- Nasiri N, Moini A, Eftekhari-Yazdi P, Karimian L, Salman-Yazdi R, Arabipoor A. Oxidative stress statues in serum and follicular fluid of women with endometriosis. Cell J. 2017;18:582-87.
- Andrade AZ, Rodrigues JK, Dib LA, Romão GS, Ferriani RA, Jordão Junior AA et al. Marcadores séricos de estresse oxidativo em mulheres inférteis com endometriose. Rev Bras Ginecol Obstet. 2010;32:279-85.
- Augoulea A, Kindis A, Karopoulou E, Tsoltos N, Kaparos G, Tsakonas E et al. Age at menarche and oxidative stress markers in women with endometriosis. SN Compr Clin Med. 2020;2:69-74.
- Vallance P, Leiper J. Cardiovascular biology of the asymmetric dimethylarginine: dimethylarginine dimethylaminohydrolase pathway. Arterioscler Thromb Vasc Biol. 2004;24:1023-30.
- Zhou S, Zhu Q, Li X, Chen C, Liu J, Ye Y et al. Asymmetric dimethylarginine and all-cause mortality: a systematic review and meta-analysis. Sci Rep. 2017;7:1-9.
- Leiper J, Murray Rust J, McDonald N, Vallance P. S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase. Proc Natl Acad Sci U S A. 2002;99:13527-532.
- Kianpour M, Nematbakhsh M, Ahmadi SM. Asymmetric dimethylarginine, nitric oxide metabolite, and estradiol levels in serum and peritoneal fluid in women with endometriosis. Iran J Nurs Midwifery Res. 2015;20:484.
Endometrioziste oksidatif stres ve apoptozla ilişkili biyobelirteçlerin düzeyleri
Yıl 2023,
Cilt: 48 Sayı: 2, 480 - 488, 02.07.2023
Dilara Ülger Özbek
,
Savaş Karakuş
,
Sevtap Bakır
Öz
Amaç: Bu çalışmada apoptoz belirteci M30 ve oksidatif stres belirteçleri malondialdehit (MDA) ve asimetrik dimetil arjinin (ADMA) endometriozis de düzeyleri incelenmiştir.
Gereç ve Yöntem: Bu prospektif vaka-kontrol çalışması, endometriozis tanısı alan 31 hasta ve 31sağlıklı kontrol grubundan oluşmaktadır. Kan serumundaki ADMA ve M30 düzeyleri enzim bağlı immünosorbent assay (ELISA) yöntemiyle, MDA düzeyleri ise spektrofotometrik yöntemle ölçüldü. Ayrıca bazı biyokimyasal parametreler ve kanser antijen (CA-125) düzeyleri de ölçüldü.
Bulgular: M30 düzeyleri endometriozis grubunda (271,5 IU/L), kontrol grubuna (371,3 IU/L) göre istatistiksel olarak daha düşük bulundu. ADMA seviyeleri endometriozis grubunda (19,3 ng/L) kontrol grubuna (12,7 ng/L) göre daha yüksekti. CA-125 düzeyleri endometriozis grubunda (65,1 U/mL) kontrol grubuna göre (19,0 U/mL) istatistiksel olarak yüksekti. MDA düzeylerinde iki grup arasında anlamlı fark yoktu. Sonuçlar disparoni, pelvik ağrı, AST ve ALP açısından istatistiksel olarak anlamlıydı.
Sonuç: Çalışmamızda hasta grubunda azalmış M30 seviyeleri endometrioziste azalmış apoptoz ile ilişkilendirildi. Oksidatif stresin artmasıyla yükselen ADMA düzeyleri hastalarda daha yüksekti. Artmış oksidatif stresin bir göstergesi olan MDA düzeyleri de hasta grubunda daha yüksek bulundu. Bu çalışma, endometriozis hastalarında ADMA, M30 ve MDA düzeylerinin bir arada yer alması açısından ilk verileri oluşturmaktadır.
Kaynakça
- Kao LGL, Giudice L. Endometriosis. Lancet. 2004;364:1789-99.
- Stratton P, Winkel C, Premkumar A, Chow C, Wilson J, Hearns-Stokes R et al. Diagnostic accuracy of laparoscopy, magnetic resonance imaging, and histopathologic examination for the detection of endometriosis. Fertil Steril. 2003;79:1078-85.
- Brosens I, Puttemans P, Campo R, Gordts S, Brosens J. Non-invasive methods of diagnosis of endometriosis. Curr Opin Obstet Gynecol. 2003;15:519-22.
- Sampson JA. Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol. 1927;14:422-69.
- Chantalat E, Valera MC, Vaysse C, Noirrit E, Rusidze M, Weyl A et al. Estrogen receptors and endometriosis. Int J Mol Sci. 2020;21:2815.
- Patel BG, Rudnicki M, Yu J, Shu Y, Taylor RN. Progesterone resistance in endometriosis: origins, consequences and interventions. Acta Obstet Gynecol Scand. 2017;96:623-32.
- Yang WC, Chen HW, Au HK, Chang CW, Huang CT, Yen YH et al. Serum and endometrial markers. Best Pract Res Clin Obstet Gynaecol. 2004;18:305-18.
- Gonçalves G, Camargo-Kosugi C, Bonetti T, Invitti A, Girão M, Silva I et al. p27 kip1 overexpression regulates VEGF expression, cell proliferation and apoptosis in cell culture from eutopic endometrium of women with endometriosis. Apoptosis. 2015;20:327-35.
- Gaben AM, Saucier Cc, Bedin M, Redeuilh Gr, Mester J. Mitogenic activity of estrogens in human breast cancer cells does not rely on direct induction of mitogen-activated protein kinase/extracellularly regulated kinase or phosphatidylinositol 3-kinase. Mol Endocrinol. 2004;18:2700-13.
- Yilmaz BD, Bulun SE. Endometriosis and nuclear receptors. Hum Reprod Update. 2019;25:473-85.
- Sansone AM, Hisrich BV, Young RB, Abel WF, Bowens Z, Blair BB et al. Evaluation of BCL6 and SIRT1 as non-invasive diagnostic markers of endometriosis. Curr Issues Mol Biol. 2021;43:1350-60.
- Koruk I, Özdemır H, Aydinli M, Bekmen N, Tarakçioğlu M, Koruk M. The relation between serum cytokeratin 18 and acute pancreatitis: can it be a serological predictive marker? Turk J Gastroenterol. 2012;23:759-63.
- Demiray M, Ulukaya EE, Arslan M, Gokgoz S, Saraydaroglu O, Ercan I et al. Response to neoadjuvant chemotherapy in breast cancer could be predictable by measuring a novel serum apoptosis product, caspase-cleaved cytokeratin 18: a prospective pilot study. Cancer Invest. 2006;24:669-76.
- Ulukaya E, Yilmaztepe A, Akgoz S, Linder S, Karadag M. The levels of caspase-cleaved cytokeratin 18 are elevated in serum from patients with lung cancer and helpful to predict the survival. Lung cancer. 2007;56:399-404.
- Meresman GF, Bilotas MA, Lombardi E, Tesone M, Sueldo C, Baranao RI. Effect of GnRH analogues on apoptosis and release of interleukin-1beta and vascular endothelial growth factor in endometrial cell cultures from patients with endometriosis. Hum Reprod. 2003;18:1767-71.
- Taylor RN, Lebovic DI, Mueller MD. Angiogenic factors in endometriosis. Ann N Y Acad Sci. 2002;955:89-100.
- Gilligan DM, Quyyumi AA, Cannon 3rd R. Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women. Circulation. 1994;89:2545-51.
- Palmer RM, Ferrige A, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327:524-26.
- Vita JA, Keaney Jr JF. Endothelial function: a barometer for cardiovascular risk. Circulation. 2002:640-42.
- Xia W, Feng W, Guan M, Yu Y, Li J, Qu X. Increased levels of asymmetric dimethylarginine and C-reactive protein are associated with impaired vascular reactivity in essential hypertension. Clin Exp Hypertens. 2010;32:43-8.
- Sydow K, Münzel T. ADMA and oxidative stress. Atheroscler Suppl. 2003;4:41-51.
- Killic E, Yazar S, Saraymen R, Hozbilge H. Serum malondialdehyde level in patients infected with Ascaris lumbricodes. World J Gastroentrol. 2003;9:2332-34.
- Jain SK. Evidence for membrane lipid peroxidation during the in vivo aging of human erythrocytes. Biochim Biophys Acta Biomembr. 1988;937:205-10.
- Gludice L. Clinical practice endometriosis. N Engl J Med. 2010;362:2389-88.
- Avant RF. Dysmenorrhea. Prim Care. 1988;15:549-59.
- Nisenblat V, Bossuyt PM, Shaikh R, Farquhar C, Jordan V, Scheffers CS et al. Blood biomarkers for the non‐invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 1996;2016.
- Kashanian M, Sariri E, Vahdat M, Ahmari M, Moradi Y, Sheikhansari N. A comparison between serum levels of interleukin-6 and CA125 in patients with endometriosis and normal women. Med J Islam Repub Iran. 2015;29:280.
- Rocha ALL RF, Taylor RN. Angiogenesis and endometriosis. Gynecol Obstet Int. 2013:1-8.
- Vaskivuo T, Stenbäck F, Karhumaa P, Risteli J, Dunkel L, Tapanainen JS. Apoptosis and apoptosis-related proteins in human endometrium. Mol Cell Endocrinol. 2000;165:75-83.
- Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35:495-516.
- Büyükgebiz O, Caferler J. Apoptoz. Sendrom. 2001;13:102-7.
- Lee KS, Chung JY, Jung YJ, Chung WY, Park JH, Sheen SS et al. The significance of caspase-cleaved cytokeratin 18 in pleural effusion. Tuberc Respir Dis. 2014;76:15-22.
- Harada T, Iwabe T, Terakawa N. Role of cytokines in endometriosis. Fertil Steril. 2001;76:1-10.
- Augoulea A, Mastorakos G, Lambrinoudaki I, Christodoulakos G, Creatsas G. The role of the oxidative-stress in the endometriosis-related infertility. Gynecol Endocrinol. 2009;25:75-81.
- Nasiri N, Moini A, Eftekhari-Yazdi P, Karimian L, Salman-Yazdi R, Arabipoor A. Oxidative stress statues in serum and follicular fluid of women with endometriosis. Cell J. 2017;18:582-87.
- Andrade AZ, Rodrigues JK, Dib LA, Romão GS, Ferriani RA, Jordão Junior AA et al. Marcadores séricos de estresse oxidativo em mulheres inférteis com endometriose. Rev Bras Ginecol Obstet. 2010;32:279-85.
- Augoulea A, Kindis A, Karopoulou E, Tsoltos N, Kaparos G, Tsakonas E et al. Age at menarche and oxidative stress markers in women with endometriosis. SN Compr Clin Med. 2020;2:69-74.
- Vallance P, Leiper J. Cardiovascular biology of the asymmetric dimethylarginine: dimethylarginine dimethylaminohydrolase pathway. Arterioscler Thromb Vasc Biol. 2004;24:1023-30.
- Zhou S, Zhu Q, Li X, Chen C, Liu J, Ye Y et al. Asymmetric dimethylarginine and all-cause mortality: a systematic review and meta-analysis. Sci Rep. 2017;7:1-9.
- Leiper J, Murray Rust J, McDonald N, Vallance P. S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase. Proc Natl Acad Sci U S A. 2002;99:13527-532.
- Kianpour M, Nematbakhsh M, Ahmadi SM. Asymmetric dimethylarginine, nitric oxide metabolite, and estradiol levels in serum and peritoneal fluid in women with endometriosis. Iran J Nurs Midwifery Res. 2015;20:484.