The preventive effect of oral EGCG in a fetal alcohol spectrum disorder mouse model.
BACKGROUND
Fetal alcohol spectrum disorder (FASD) is a challenging public health problem. Previous studies have found an association between FASD and oxidative stress. In the present study, we assessed the role of oxidative stress in ethanol-induced embryonic damage and the effect of (-)-epigallocatechin-3-gallate (EGCG), a powerful antioxidant extracted from green tea, on the development of FASD in a murine model.


METHODS
Pregnant female mice were given intraperitoneal ethanol (25%, 0.005 to 0.02 ml/g) on gestational day 8 (G8) to establish the FASD model. On G10.25, mice were sacrificed and embryos were collected and photographed to determine head length (HL), head width (HW), and crown rump length (CRL). For mice given EGCG, administration was through a feeding tube on G7 and G8 (dose: 200, 300, or 400 mg/kg/d, the total amount for a day was divided into 2 equal portions). G10.25 embryos were evaluated morphologically. Brain tissues of G9.25 embryos were used for RT-PCR and western blotting of neural marker genes and proteins and detection of oxidative stress indicators.


RESULTS
Administration of ethanol to pregnant mice on G8 led to the retardation of embryonic growth and down-regulation of neural marker genes. In addition, administration of ethanol (0.02 ml/g) led to the elevation of oxidative stress indicators [hydrogen peroxide (H₂O₂) and malondialdehyde (MDA)]. Administration of EGCG on G7 and G8 along with ethanol on G8 ameliorated the ethanol-induced growth retardation. Mice given EGCG (400 mg/kg/d) along with ethanol had embryo sizes and neural marker genes expression similar to the normal controls. Furthermore, EGCG (400 mg/kg on G7 and G8) inhibited the increase in H₂O₂ and MDA.


CONCLUSIONS
In a murine model, oxidative stress appears to play an important role in ethanol-induced embryonic growth retardation. EGCG can prevent some of the embryonic injuries caused by ethanol.
Long
Ling
L
Department of Neurology, The Second Affiliated Hospital, Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou, China.
Li
Yi
Y
Wang
Yi Dong
YD
He
Qing Yu
QY
Li
Mei
M
Cai
Xiao Dong
XD
Peng
Kou
K
Li
Xiang Pen
XP
Xie
Dan
D
Wen
Yan Ling
YL
Yin
De Ling
DL
Peng
Ying
Y
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D047108:Embryonic Development / Q000187:drug effects; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000188:drug therapy* / Q000473:pathology; D005333:Fetus / Q000473:pathology; D005819:Genetic Markers; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007231:Infant, Newborn; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000502:physiology; D011247:Pregnancy; D017382:Reactive Oxygen Species; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013662:Tea
D002492:Central Nervous System Depressants; D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013662:Tea; D000431:Ethanol; D008315:Malondialdehyde; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate