Prematüre Bebeklerde Oksidan Hasarın Yol Açtığı Problemler
ÖzSerbest radikaller (FR), sürekli olarak endojen ve eksojen mekanizmalarla üretilen, kararsız, kısa ömürlü ve oldukça reaktif moleküllerdir. Canlı organizmalardaaz miktarda serbest radikal üretilir ve normal hücre reaksiyonları ve hücre büyümesi için gereklidir. Yenidoğan döneminde hipoksi, iskemi, iskemi reperfüzyonu, hiperoksi, inflamasyon, mitokondriyal yetmezlik, proteine bağlı olmayan demir aşırı FR üretiminden sorumludur. FR'lerin tehlikeli etkileri, çok kararsız molekül olmaözelliklerine ve hücre membranları, proteinler, polisakaritler, nükleik asitlerden oluşan çoklu doymamış yağ asitleri ile reaksiyona girebilme yetenekleri ile bağlantılıdır ve bu da hücre içinde işlevsel değişikliklere neden olur. Preterm bebeklerde antioksidan savunmanın yetersizliği ve reaktif oksijen türlerinin aşırı miktarda üretimi, periventriküler lökomalazi, intraventriküler kanama, bronkopulmoner displazi,prematüre retinopatisi ve nekrotizan enterokolit gibi yenidoğan hastalıklarının oluşumunda rol oynar. Bu yazıda pretermlerdeki neonatal hastalıkların patogenezinde serbest radikallerin etkisi tartışılmıştır.
Problems with Oxidative Damage in Premature Infants
AbstractFree radicals (FRs) are unstable, short lived, and highly reactive molecules thatare continuously generated by endogenous and exogenous mechanisms Small amounts of free radicals are generated continuously in living organisms and are necessary for normal cell reactions and cell growth. In neonatal period, hypoxia, ische-mia, ischemia reperfusion, hyperoxia, inflammation, mitochondrial impairment, presence of nonprotein bound iron are responsible of excessive FRs production. The dangerous effects of FRs are linked to their property of being very unstable moleculesand their ability to react with polyunsaturated fatty acids of cell membranes, proteins, polysaccharides, nucleic acids, causing functional alterations within the cell. Excessive production of reactive oxygen species associated with deficient antioxidant defenses in preterm infants have been implicated in neonatal diseases such as periventricular leukomalacia, intraventricular hemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity, and necrotizing enterocolitis The effect of free radicals in the pathogenesis of preterm neonatal diseases are discussed in this review.
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- Kaynaklar
1.Perrone S, Tataranno ML, Stazzoni G,Buonocore G. Oxi-dative stress and free radicals related diseases of the new-born. Advances in Bioscience and Biotechnology, 2012; 3:1043-1050.
2.Buonocore, G., Perrone, S. And Tataranno, M.L. (2010) Oxy-gen toxicity: Chemistry and biology of reactive oxy- gen spe-cies. Seminars in Fetal and Neonatal Medicine, 15, 186-190.
3.Davies, K.J. (2000) Oxidative stress, antioxidant defenses, anddamage removal, repair, and replacement systems. IUBMBLife, 2000;50,:279-289.
4.Perrone S, Tataranno ML Negro S et al The Free Radical Di-seases of Newborn J Pediatr Biochem 2016;6:73–78.
5.Trindade CE, Rugolo LM Free Radicals and Neonatal Disea-ses Neoreviews 2007;8;e522
6.Buonocore G, Perrone S, Longini M, et al. Oxidative stressin preterm neonates at birth and on the seventh day of life. Pe-diatr Res. 2002;52:46–49 6
7.Thibeault DW. The precarious antioxidant defenses of the pre-term infant. Am J Perinatol. 2000;4:167–181
8.Ozsurekci Y , Aykac KOxidative Stress Related Diseases inNewborns.Oxid Med Cell Longev. 2016;2016:2768365. doi:10.1155/2016/2768365
9.Buonocore G, Perrone S, Longini M, et al. Oxidative stressin preterm neonates at birth and on the seventh day of life. Pe-diatr Res 2002;52(1):46–49
10.Volpe JJ. Perinatal brain injury: from pathogenesis to neu-roprotection. Ment Retard Dev Disabil Res Rev2001;7(1):56–64
11.McCrea HJ, Ment LR. The diagnosis, management, and post-natal prevention of intraventricular hemorrhage in the pre-term neonate. Clin Perinatol 2008;35(4):777–792
12.Gandhi S, Abramov AY. Mechanism of oxidative stress in neu-rodegeneration. Oxid Med Cell Longev 2012;2012:428010
13.Baburamani AA, Ek CJ, Walker DW, Castillo-Melendez M.Vulnerability of the developing brain to hypoxic–ischemic da-mage: contribution of the cerebral vasculature to injury andrepair? Front Physiol 2012;3:424
14.Kuwano T, Nakao S, Yamamoto H, et al. Cyclooxygenase 2is a key enzyme for inflammatory cytokine-induced angioge-nesis. FASEB J 2004;18(2):300–310
15.UlfigN, Bohl J,Neudörfer F, Rezaie P. Brainmacrophages and-microglia in human fetal hydrocephalus. Brain Dev2004;26(5):307–315
16.Folkerth RD, Keefe RJ, Haynes RL, Trachtenberg FL, VolpeJJ, Kinney HC. Interferon-gamma expression in periventri-cular leukomalacia in the human brain. Brain Pathol2004;14(3):265–274
17.Lee JW, Davis JMFuture applications of antioxidants in pre-mature infants. Curr Opin Pediatr. 2011 Apr;23(2):161-6
18.Volpe JJ. Neurobiology of periventricular leukomalacia in thepremature infant Pediatric Research 2001:50;553-562
19.Rivera JC, Sapieha P, Joyal JS, et al. Understanding retino-pathy of prematurity: update on pathogenesis. Neonatology2011;100(4): 343–353
20.Ushio-Fukai M. Redox signaling in angiogenesis: role ofNADPH oxidase. Cardiovasc Res 2006;71(2):226–235
21.Perrone S, Vezzosi P, Longini M, et al. Biomarkers of oxida-tive stress in babies at high risk for retinopathy of prematu-rity. Front Biosci (Elite Ed) 2009;1:547–552
22.Buonocore G, Perrone S, Longini M, Terzuoli L, Bracci R. To-tal hydroperoxide and advanced oxidation protein productsin preterm hypoxic babies. Pediatr Res 2000;47(2):221–224
23.Jo N, Mailhos C, Ju M, et al. Inhibition of platelet-derived growthfactor B signaling enhances the efficacy of anti-vascular endot-helial growth factor therapy in multiple models of ocular neo-vascularization. Am J Pathol 2006;168(6): 2036 –2053
24.Joung KE, Kim HS, Lee J, et al. Correlation of urinary inflam-matory and oxidative stress markers in very low birth weightinfants with subsequent development of bronchopulmonarydysplasia. Free Radic Res 2011;45(9):1024–1032
25.Saugstad OD. Bronchopulmonary dysplasia-oxidative stressandantioxidants. Semin Neonatol 2003;8(1):39–49
26.Haagsman HP. Interactions of surfactant protein Awith pat-hogens. Biochim Biophys Acta 1998;1408(2–3):264–277
27.Inder TE, Graham P, Sanderson K, Taylor BJ. Lipid peroxi-dation as a measure of oxygen free radical damage in the verylow birthweight infant. Arch Dis Child Fetal Neonatal Ed1994;70(2):F107–F111
28.Varsila E, Pesonen E, Andersson S. Early protein oxidationin the neonatal lung is related to development of chronic lungdisease. Acta Paediatr 1995;84(11):1296–1299
29.S. M. Gephart, J. M. McGrath, J. A. Effken, and M. D. Hal-pern, Necrotizing enterocolitis risk state of the science,” Ad-vances in Neonatal Care, 2012 ; 12: 77–87..
30.Lee JH. An update on necrotizing enterocolitis: pathogene-sis and preventive strategies. Korean J Pediatr2011;54(9):368–372
31.Nankervis CA, Giannone PJ, Reber KM. The neonatal intes-tinal,vasculature: contributing factors to necrotizing entero-colitis. Semin Perinatol 2008;32(2):83–91