Melatonin inhibits oxidative stress and apoptosis in fetal brains of hyperhomocysteinemic rat dams

被引:37
作者
Baydas, Giyasettin [1 ]
Koz, Sema T.
Tuzcu, Mehmet
Etem, Ebru
Nedzvetsky, Viktor S.
机构
[1] Firat Unit, Fac Med, Dept Physiol, TR-23119 Elazig, Turkey
[2] Firat Univ, Fac Sci, Dept Biol, Elazig, Turkey
[3] Firat Univ, Fac Med, Dept Med Biol, Elazig, Turkey
[4] Dnetpropetrosvk Natl Univ, Fac Biol, Dept Biophys & Biochem, Dnepropetrovsk, Ukraine
关键词
apoptosis; hyperhomocysteinemia; melatonin; oxidative stress; pup brain;
D O I
10.1111/j.1600-079X.2007.00465.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Moderate hyperhomocysteinemia is a risk factor for neurodegenerative diseases and complications during pregnancy. Increased homocysteine levels during pregnancy may elevate developmental risk on fetal brain structure and function. However, little is known about the mechanism of action of homocysteine on the degeneration of the fetal brain. Hence in this study, we examined the effects of maternal hyperhomocysteinemia on oxidative stress and apoptosis in brain tissues and investigated whether administration of melatonin to the mother would prevent homocysteine-induced oxidative cerebral damage in pups. Hyperhomocysteinemia was induced in female rats by administration of methionine at a dose of 1 g/kg body weight dissolved in drinking water during pregnancy. Some animals received methionine plus 10 mg/kg/day melatonin subcutaneously throughout pregnancy. After delivery, the level of lipid peroxidation (malondialdehyde + 4-hydroxyalkenals) was determined in different subfractions of pup brains. Furthermore, DNA fragmentation, levels of Bcl-2 protein and p53 mRNA expression were determined to evaluate apoptosis. Significant elevation was found in the levels of lipid peroxidation in subcellular fractions of the brain of pups of hyperhomocysteinemic dams. Increased DNA fragmentation and p53 mRNA expression was observed in the brain of pups of homocysteine-treated rats, while a significant reduction was seen in the levels of anti-apoptotic Bcl-2 levels. Melatonin administration prevented markers of oxidative stress and biochemical signs of apoptosis. In conclusion, therapeutic administration of melatonin protects against the induction of oxidative stress and neural tissue injury and might prevent congenital malformations of fetal brain caused by maternal hyperhomocysteinemia.
引用
收藏
页码:225 / 231
页数:7
相关论文
共 47 条
[1]   Plasma homocysteine in late pregnancies complicated with preeclampsia and in newborns [J].
Baksu, A ;
Taskin, M ;
Goker, N ;
Baksu, B ;
Uluocak, A .
AMERICAN JOURNAL OF PERINATOLOGY, 2006, 23 (01) :31-35
[2]   Melatonin prevents oxidative stress and inhibits reactive gliosis induced by hyperhomocysteinemia in rats [J].
Baydas, G ;
Ozer, M ;
Yasar, A ;
Koz, ST ;
Tuzcu, M .
BIOCHEMISTRY-MOSCOW, 2006, 71 (Suppl 1) :S91-S95
[3]   Melatonin inhibits neural apoptosis induced by homocysteine in hippocampus of rats via inhibition of cytochrome c translocation and caspase-3 activation and by regulating pro- and anti-apoptotic protein levels [J].
Baydas, G ;
Reiter, RJ ;
Akbulut, M ;
Tuzcu, M ;
Tamer, S .
NEUROSCIENCE, 2005, 135 (03) :879-886
[4]   Melatonin improves learning and memory performances impaired by hyperhomocysteinemia in rats [J].
Baydas, G ;
Özer, M ;
Yasar, A ;
Tuzcu, M ;
Koz, ST .
BRAIN RESEARCH, 2005, 1046 (1-2) :187-194
[5]   Inhibitory effects of melatonin on neural lipid peroxidation induced by intracerebroventricularly administered homocysteine [J].
Baydas, G ;
Kutlu, S ;
Naziroglu, M ;
Canpolat, S ;
Sandal, S ;
Ozcan, M ;
Kelestimur, H .
JOURNAL OF PINEAL RESEARCH, 2003, 34 (01) :36-39
[6]   A novel role for melatonin: regulation of the expression of cell adhesion molecules in the rat hippocampus and cortex [J].
Baydas, G ;
Nedzvetsky, VS ;
Nerush, PA ;
Kirichenko, SV ;
Demchenko, HM ;
Reiter, RJ .
NEUROSCIENCE LETTERS, 2002, 326 (02) :109-112
[7]   Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: Implications for cancer and neuronal damage [J].
Blount, BC ;
Mack, MM ;
Wehr, CM ;
MacGregor, JT ;
Hiatt, RA ;
Wang, G ;
Wickramasinghe, SN ;
Everson, RB ;
Ames, BN .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (07) :3290-3295
[8]   Down-regulation of mammalian mitochondrial RNAs during oxidative stress [J].
Crawford, DR ;
Wang, YH ;
Schools, GP ;
Kochheiser, J ;
Davies, KJA .
FREE RADICAL BIOLOGY AND MEDICINE, 1997, 22 (03) :551-559
[9]  
Deng WG, 2004, WORLD J GASTROENTERO, V10, P46
[10]   Lithium inhibits Aβ-induced stress in endoplasmic reticulum of rabbit hippocampus but does not prevent oxidative damage and tau phosphorylation [J].
Ghribi, O ;
Herman, MM ;
Savory, J .
JOURNAL OF NEUROSCIENCE RESEARCH, 2003, 71 (06) :853-862