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Preeklamptik Anne ve Bebeklerinde Asimetrik Dimetil Arjinin ve Oksidan/Antioksidan Düzeyi

Year 2023, Volume: 7 Issue: 2, 112 - 119, 31.08.2023
https://doi.org/10.29058/mjwbs.1051152

Abstract

Amaç: Preeklampsili gebelerde asimetrik dimetilarjinin (ADMA) düzeyinin sağlıklı gebelere göre anlamlı oranda yüksek olduğu,
ADMA yüksekliğinin preeklampsinin klinik işaretlerinden daha önce geliştiği ve ADMA’nın preeklampsinin patogenezinde rol oynadığı
düşünülmektedir. Bu çalışmada, sağlıklı ve preeklamptik gebeler ve bebeklerinden alınan serum ADMA, nitrik oksit metaboliti total nitrit
ve nitrat (NOx), arjinin ve total antioksidan kapasite (TAK) ve plasenta örneklerindeki düzeylerinin preeklampsi ile ilişkili olup olmadığı, bu
belirteçlerle preklampsinin önceden tespit edilip edilemeyeceği ve bunun sonucunda anne ve bebekte gelişebilecek olası sorunların önlenip
önlenemeyeceğinin araştırılması amaçlanmıştır.
Gereç ve Yöntemler: Zonguldak Bülent Ecevit Üniversitesi Kadın Doğum Servisinde takip edilen 62 gebe ve bebeği çalışmaya alınarak
preeklampsisi olan 31 gebe ve bebeği Grup I, hasta grubunu; preeklamptik olmayan 31 gebe ve bebeği ise Grup II, kontrol grubunu
oluşturdu. Çalışmada değerlendirilmek üzere annelerden doğumdan önce, korddan doğum sırasında, bebeklerden doğumdan sonraki ilk
24 saat içinde kan örnekleri ve her gebeden plasenta örneği alındı. Preeklampsi tanısı olan ve olmayan annelerin yaşı, kilosu, ilk gebelik
durumu, gebelik süreleri, sistolik ve diastolik kan basıncı değerleri, bebeklerin ise doğum ağırlıkları, cinsiyetleri, tedavisi süresince gelişen
problem ve komplikasyonları, klinik ve laboratuar özellikleri, prognozları, ADMA, arjinin, NOx ve TAK düzeyleri incelendi.
Bulgular: İki grup karşılaştırıldığında prognozu etkileyebilecek antenatal faktörler açısından anlamlı fark yoktu. Preeklamptik anne grubunda
ADMA düzeyinin anlamlı olarak yüksek (p<0.001), arjinin değerinin anlamlı olarak düşük olduğu (p=0.001), NOx düzeyi ve TAK arasında ise
fark olmadığı saptandı. Kord kanı değerlendirildiğinde preeklamptik grupta ADMA düzeyinin anlamlı olarak yüksek (p=0.001), NOx değerinin
anlamlı olarak düşük olduğu (p=0.017), arjinin düzeyleri ve total antioksidan kapasite arasında fark olmadığı saptandı. Preeklamptik grup
plasentasında ADMA ve arjinin değerlerinin anlamlı olarak yüksek olduğu (p<0.001), total antioksidan kapasite düzeyinin düşük olduğu
görüldü (p=0.004). NOx değerinin iki grup arasında farklı olmadığı saptandı. Bebek kanları karşılaştırıldığında anne, kord kanı ve plasenta
örneklerinin aksine kontrol grubunda ADMA değerinin anlamlı yüksek olduğu (p=0.009), preeklamptik grupta arjininin anlamlı olarak yüksek
olduğu (p=0.041), iki grup arasında NOx ve TAK açısından fark olmadığı saptandı.
Sonuç: Bu çalışmada preeklamptik anne grubunda serum ADMA düzeyinin literatür ile uyumlu olarak arttığı saptandı. Çalışma literatürdeki
preeklamptik hastalarda nitrik oksit sentezinin azaldığı tezini desteklememektedir. Yüksek risk altındaki kadınların erken dönemde
belirlenmesinde ADMA yeni bir risk belirleyicisi olarak kullanılabilir.

Supporting Institution

zonguldak bülent ecevit üniverstesi tıp fakültesi bap

Project Number

2013/02-4

Thanks

Prof.Dr.İnan İlker Arıkan,Prof.Dr.Murat Can

References

  • 1. Pijnenborg R, Roberston WB, Brosens I, Dixon G. Trophoblastic invasion and the establishment of haemochorial placentation in man and laboratory animals. Placenta 1981; 2: 71-91.
  • 2. Prefumo F, Sebire NJ, Thilaganathan B. Decreased endovascular trophoblast invasion in first trimester pregnancies with high-resistance uterine artery Doppler indices. Hum. Reprod 2004; 19: 206-9.
  • 3. Buhimschi IA, Saade GR, Chwalisz K, Garfield RE. The nitric oxide pathway in preeclampsia: pathophysiological implications. Hum Reprod Update 1998; 4(1): 25-42.
  • 4. Rosselli M, Keller PJ, Dubey RK. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Hum Reprod Update 1998;4(1):3-24.
  • 5. Lowe DT. Nitric oxide dysfunction in the pathophysiology of preeclampsia. Nitric Oxide 2000;4(4):441-458.
  • 6. Lentz SR, Rodionov RN, Dayal S. Hyperhomocysteinemia, endothelial dysfunction, and cardiovascular risk: the potential role of ADMA. Atherosclerosis Supplements 2003;4:61-65.
  • 7. Verit FF, Erel O, Sav M, Celik N, Cadirci D. Oxidative stress is associated with clinical severity of nausea and vomiting of pregnancy. Am J Perinatol 2007;24(9):545-548.
  • 8. Eiben B, Glaubitz R. First-trimester screening: an overview. J Histochem Cytochem 2005;53:281-283.
  • 9. Cortas NK, Wakid NW. Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 1990;36(8 Pt 1):1440-1443.
  • 10. Fickling SA, Williams D, Vallance P, Nussey SS, Whitley GS. Plasma concentrations of endogenous inhibitor of nitric oxide synthesis in normal pregnancy and preeclampsia. Lancet 1993;342:242-243.
  • 11. Savvidou MD, Hingorani AD, Tsikas D, Frölich JC, Vallance P, Nicolasides KH. Endothelial dysfunction and raised plasma concentration of asymmetric dimethylarjinine in pregnant woman who subsequently develop preeclampsia. Lancet 2003;361:1511-1517.
  • 12. Speer PD, Powers RW, Frank MP, Harger G, Markovic N, Roberts JM. Elevated asymmetric dimethylarginine concentrations precede clinical preeclampsia, but not pregnancies with small-for-gestational-age infants. Am J Obstet Gynecol 2008;198:112.
  • 13. Kim YJ, Park HS, Lee HY. Reduced Larginine level and decreased placental eNOS activity in preeclampsia. Placenta 2006;27(4-5):438-444.
  • 14. Tsukahara H, Ohta N, Tokuriki S, Nishijima K, Kotsuji F, Kawakami H, Ohta N, Sekine K, Nagasaka H, Mayumi M. Determination of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, in umbilical blood. Metabolism 2008;57(2):215-220.
  • 15. Carcillo JA, Cunnion RE. Septic shock. Crit Care Clin 1997;13:553.
  • 16. Argaman Z, Young VR, Noviski N, Castillo-Rosas L, Lu XM, Zurakowski D, Cooper M, Davison C, Tharakan JF, Ajami A, Castillo L. Arginine and nitric oxide metabolism in critically ill septic pediatric patients. Crit Care Med 2003;31(2):591-597.
  • 17. Böger RH, Bode-Böger SM. The clinical pharmacology of L-arginine. Annu Rev Pharmacol Toxicol 2001;41:79.
  • 18. Noris M, Todeschini M, Cassis P, Pasta F, Cappellini A, Bonazzola S, Macconi D, Maucci R, Porrati F, Benigni A, Picciolo C, Remuzzi G. L-arginine depletion in preeclampsia orients nitric oxide synthase toward oxidant species. Hypertension 2004;43(3):614-622.
  • 19. Böger RH, Bode-Böger SM, Sydow K, Heistad DD, Lentz SR. Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in monkeys with hyperhomocyst(e)inemia or hypercholesterolemia. Arterioscler Thromb Vasc Biol 2000;20:1557-1564.
  • 20. Sandra T. Davidge PhD. Christopher P. Stranko BS and James M. Urine but not plasma nitric oxide metabolites are decreased in women with preeclampsia. Am J Obstet Gynecol 1996;174:1008-1013.
  • 21. Akyol S,Alıcı Ö,Altuntaş A , Pehlivan S , S. Kurşunlu F, Alaçam H. Asymmetric dimethyl arginine (ADMA) induces acute tubular necrosis in rats. Yeni Tıp Dergisi 2015;32:13-16.
  • 22. Budak Y, Işıtmangil G, İnal Ş. Preeklamptik hastalarda antioksidan aktivite ve lipid peroksidasyonu arasındaki dengenin irdelenmesi. İst Tıp Fak Mecmuası 2004;67:3.
  • 23. Kharb S: Total free radical trapping antioxidant potential in preeclampsia. Int J Gynaecol 2000;69:23.
  • 24. Shaarawy M, Aref A, Salem ME, Sbeiba M: Radical scavenging antioxidants in pre-eclampsia and eclampsia. Int J Gynaecol Obstet 1998;60:123.
  • 25. Wijnberger LDE, Krediet TG, Visser GHA, Van Bel F, Egberts J. Early neonatal antioxidant capacity after preexisting impaired placental function. Early Hum Dev 2003;71:111-116.
  • 26. Saugstad OD. Mechanisms of tissue injury by oxygen radicals: implications for neonatal disease. Acta Paediatr 1996;85:1-4.
  • 27. Moison RMW, De Beaufort AJ, Haasnoot AA, Dubbelman TMAR, Van Zoeren-Grobben D, Berger HM. Uric acid and ascorbic acid redox ratios in plasma and tracheal aspirate of preterm babies with acute and chronic lung disease. Free Radic Biol Med 1997;23:226-234.

Asymmetric Dimethyl Arginine and Oxidant/Antioxidant Level in Preeclamptic Mothers and Their Babies

Year 2023, Volume: 7 Issue: 2, 112 - 119, 31.08.2023
https://doi.org/10.29058/mjwbs.1051152

Abstract

Aim: It is thought that asymmetric dimethyl arginine(ADMA) level is significantly higher in pregnant
women with preeclampsia compared to healthy pregnant women, ADMA elevation develops before
the clinical signs of preeclampsia, and ADMA plays a role in the pathogenesis of preeclampsia. In this
study, it was aimed to investigate whether serum ADMA, total nitrite and nitrate (NOx), arginine and
total antioxidant capacity (TAC) and levels in placenta samples taken from healthy and preeclamptic
pregnant women and their babies are associated with preeclampsia, whether preeclampsia can be
detected beforehand with these markers, and whether possible problems that may develop in the
mother and baby can be prevented as a result.
Material and Methods: 62 pregnant women and their babies who were followed up in Zonguldak
Bülent Ecevit University obstetrics service are divided two groups; 31 preeclamptic pregnant and babies
(Group I), formed Patient group; 31 pregnant and babies without preeclampsia (Group II), formed
Control Group. Blood samples were obtained from mothers before birth, from the cord during birth, from
babies in first 24 hours after birth and placenta samples were obtained from each pregnant to evaluate
in the study. Age, weight, initial pregnancy state, pregnancy period, systolic and diastolic blood pressure
levels of mothers with and without pre-eclampsia diagnosis, while birth weights, genders, problems and
complications during treatment process, clinic and laboratory properties, prognosis, ADMA, arginine,
NOx and TAC levels of babies were examined in this study.
Results: There was no significant difference between two groups about antenatal factors that effect
on prognosis. In the comparison of blood values, ADMA level of preeclamptic group was significantly
higher (p<0.001) while arginine value was significantly lower (p=0.001) than control group, there was
no significant difference in NOx level and TAC between two groups. In the evaluation of cord ADMA
level of preeclamptic group was significantly higher (p=0.001) while nitric oxide value was significantly
lower (p=0.017) than control group and there was no significant difference in arginine and TAC. Values
which are studied in placenta samples showed that ADMA and arginine values were significantly high
(p<0.001) total antioxidant capacity level was low (p=0.004) in placenta of preeclamptic group. There
was no difference in NOx value of two groups. In the consideration of data of babies, mean pregnancy
weeks and genders were similar. Against the values of samples from mother, cord and placenta, when
baby blood was compared, ADMA value of control group was significantly high (p=0.009) while arginine
value of preeclamptic group was significantly high (p=0.041) and there was no difference between two
groups about their NOx and TAC.
Conclusion: In this study, it is determined that serum ADMA level of preeclamptic mother group increases in accordance with literature
values. This study does not support the decrease of nitric oxide synthesis thesis in preeclamptic patients as mentioned in literature. To
determine the women with the high risk in the early period, the asymmetric dimethyl arginine may be used as the new risk decisive.

Project Number

2013/02-4

References

  • 1. Pijnenborg R, Roberston WB, Brosens I, Dixon G. Trophoblastic invasion and the establishment of haemochorial placentation in man and laboratory animals. Placenta 1981; 2: 71-91.
  • 2. Prefumo F, Sebire NJ, Thilaganathan B. Decreased endovascular trophoblast invasion in first trimester pregnancies with high-resistance uterine artery Doppler indices. Hum. Reprod 2004; 19: 206-9.
  • 3. Buhimschi IA, Saade GR, Chwalisz K, Garfield RE. The nitric oxide pathway in preeclampsia: pathophysiological implications. Hum Reprod Update 1998; 4(1): 25-42.
  • 4. Rosselli M, Keller PJ, Dubey RK. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Hum Reprod Update 1998;4(1):3-24.
  • 5. Lowe DT. Nitric oxide dysfunction in the pathophysiology of preeclampsia. Nitric Oxide 2000;4(4):441-458.
  • 6. Lentz SR, Rodionov RN, Dayal S. Hyperhomocysteinemia, endothelial dysfunction, and cardiovascular risk: the potential role of ADMA. Atherosclerosis Supplements 2003;4:61-65.
  • 7. Verit FF, Erel O, Sav M, Celik N, Cadirci D. Oxidative stress is associated with clinical severity of nausea and vomiting of pregnancy. Am J Perinatol 2007;24(9):545-548.
  • 8. Eiben B, Glaubitz R. First-trimester screening: an overview. J Histochem Cytochem 2005;53:281-283.
  • 9. Cortas NK, Wakid NW. Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 1990;36(8 Pt 1):1440-1443.
  • 10. Fickling SA, Williams D, Vallance P, Nussey SS, Whitley GS. Plasma concentrations of endogenous inhibitor of nitric oxide synthesis in normal pregnancy and preeclampsia. Lancet 1993;342:242-243.
  • 11. Savvidou MD, Hingorani AD, Tsikas D, Frölich JC, Vallance P, Nicolasides KH. Endothelial dysfunction and raised plasma concentration of asymmetric dimethylarjinine in pregnant woman who subsequently develop preeclampsia. Lancet 2003;361:1511-1517.
  • 12. Speer PD, Powers RW, Frank MP, Harger G, Markovic N, Roberts JM. Elevated asymmetric dimethylarginine concentrations precede clinical preeclampsia, but not pregnancies with small-for-gestational-age infants. Am J Obstet Gynecol 2008;198:112.
  • 13. Kim YJ, Park HS, Lee HY. Reduced Larginine level and decreased placental eNOS activity in preeclampsia. Placenta 2006;27(4-5):438-444.
  • 14. Tsukahara H, Ohta N, Tokuriki S, Nishijima K, Kotsuji F, Kawakami H, Ohta N, Sekine K, Nagasaka H, Mayumi M. Determination of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, in umbilical blood. Metabolism 2008;57(2):215-220.
  • 15. Carcillo JA, Cunnion RE. Septic shock. Crit Care Clin 1997;13:553.
  • 16. Argaman Z, Young VR, Noviski N, Castillo-Rosas L, Lu XM, Zurakowski D, Cooper M, Davison C, Tharakan JF, Ajami A, Castillo L. Arginine and nitric oxide metabolism in critically ill septic pediatric patients. Crit Care Med 2003;31(2):591-597.
  • 17. Böger RH, Bode-Böger SM. The clinical pharmacology of L-arginine. Annu Rev Pharmacol Toxicol 2001;41:79.
  • 18. Noris M, Todeschini M, Cassis P, Pasta F, Cappellini A, Bonazzola S, Macconi D, Maucci R, Porrati F, Benigni A, Picciolo C, Remuzzi G. L-arginine depletion in preeclampsia orients nitric oxide synthase toward oxidant species. Hypertension 2004;43(3):614-622.
  • 19. Böger RH, Bode-Böger SM, Sydow K, Heistad DD, Lentz SR. Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in monkeys with hyperhomocyst(e)inemia or hypercholesterolemia. Arterioscler Thromb Vasc Biol 2000;20:1557-1564.
  • 20. Sandra T. Davidge PhD. Christopher P. Stranko BS and James M. Urine but not plasma nitric oxide metabolites are decreased in women with preeclampsia. Am J Obstet Gynecol 1996;174:1008-1013.
  • 21. Akyol S,Alıcı Ö,Altuntaş A , Pehlivan S , S. Kurşunlu F, Alaçam H. Asymmetric dimethyl arginine (ADMA) induces acute tubular necrosis in rats. Yeni Tıp Dergisi 2015;32:13-16.
  • 22. Budak Y, Işıtmangil G, İnal Ş. Preeklamptik hastalarda antioksidan aktivite ve lipid peroksidasyonu arasındaki dengenin irdelenmesi. İst Tıp Fak Mecmuası 2004;67:3.
  • 23. Kharb S: Total free radical trapping antioxidant potential in preeclampsia. Int J Gynaecol 2000;69:23.
  • 24. Shaarawy M, Aref A, Salem ME, Sbeiba M: Radical scavenging antioxidants in pre-eclampsia and eclampsia. Int J Gynaecol Obstet 1998;60:123.
  • 25. Wijnberger LDE, Krediet TG, Visser GHA, Van Bel F, Egberts J. Early neonatal antioxidant capacity after preexisting impaired placental function. Early Hum Dev 2003;71:111-116.
  • 26. Saugstad OD. Mechanisms of tissue injury by oxygen radicals: implications for neonatal disease. Acta Paediatr 1996;85:1-4.
  • 27. Moison RMW, De Beaufort AJ, Haasnoot AA, Dubbelman TMAR, Van Zoeren-Grobben D, Berger HM. Uric acid and ascorbic acid redox ratios in plasma and tracheal aspirate of preterm babies with acute and chronic lung disease. Free Radic Biol Med 1997;23:226-234.
There are 27 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research Article
Authors

Sedef Narin Tongal 0000-0002-4937-4949

İ.etem Pişkin 0000-0002-1561-6639

Cumhur Aydemir 0000-0001-5178-7403

İnan İlker Arıkan 0000-0001-6574-9977

Murat Can 0000-0002-1539-3973

Project Number 2013/02-4
Publication Date August 31, 2023
Acceptance Date March 13, 2023
Published in Issue Year 2023 Volume: 7 Issue: 2

Cite

Vancouver Narin Tongal S, Pişkin İ, Aydemir C, Arıkan İİ, Can M. Asymmetric Dimethyl Arginine and Oxidant/Antioxidant Level in Preeclamptic Mothers and Their Babies. Med J West Black Sea. 2023;7(2):112-9.

Medical Journal of Western Black Sea is a scientific publication of Zonguldak Bulent Ecevit University Faculty of Medicine.

This is a refereed journal, which aims at achieving free knowledge to the national and international organizations and individuals related to medical sciences in publishedand electronic forms.

This journal is published three annually in April, August and December.
The publication language of the journal is Turkish and English.