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The Preventive Effect of Oral EGCG in a Fetal Alcohol Spectrum Disorder Mouse Model

Authors

  • Ling Long,

    1. From the Departments of Neurology (LL, YL, YDW, ML, XDC, KP, XPL, YP) and Ultrasonography (YLW), The Second Affiliated Hospital, Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou, China; Institute of Life and Health Engineering (QYH), Jinan University, No. 601, West Huangpu Road, Guangzhou, China; State Key Laboratory of Oncology in South China (DX), Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou, China; and Department of Internal Medicine (DLY), James Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, U.S.A.
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  • Yi Li,

    1. From the Departments of Neurology (LL, YL, YDW, ML, XDC, KP, XPL, YP) and Ultrasonography (YLW), The Second Affiliated Hospital, Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou, China; Institute of Life and Health Engineering (QYH), Jinan University, No. 601, West Huangpu Road, Guangzhou, China; State Key Laboratory of Oncology in South China (DX), Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou, China; and Department of Internal Medicine (DLY), James Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, U.S.A.
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  • Yi Dong Wang,

    1. From the Departments of Neurology (LL, YL, YDW, ML, XDC, KP, XPL, YP) and Ultrasonography (YLW), The Second Affiliated Hospital, Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou, China; Institute of Life and Health Engineering (QYH), Jinan University, No. 601, West Huangpu Road, Guangzhou, China; State Key Laboratory of Oncology in South China (DX), Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou, China; and Department of Internal Medicine (DLY), James Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, U.S.A.
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  • Qing Yu He,

    1. From the Departments of Neurology (LL, YL, YDW, ML, XDC, KP, XPL, YP) and Ultrasonography (YLW), The Second Affiliated Hospital, Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou, China; Institute of Life and Health Engineering (QYH), Jinan University, No. 601, West Huangpu Road, Guangzhou, China; State Key Laboratory of Oncology in South China (DX), Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou, China; and Department of Internal Medicine (DLY), James Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, U.S.A.
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  • Mei Li,

    1. From the Departments of Neurology (LL, YL, YDW, ML, XDC, KP, XPL, YP) and Ultrasonography (YLW), The Second Affiliated Hospital, Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou, China; Institute of Life and Health Engineering (QYH), Jinan University, No. 601, West Huangpu Road, Guangzhou, China; State Key Laboratory of Oncology in South China (DX), Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou, China; and Department of Internal Medicine (DLY), James Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, U.S.A.
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  • Xiao Dong Cai,

    1. From the Departments of Neurology (LL, YL, YDW, ML, XDC, KP, XPL, YP) and Ultrasonography (YLW), The Second Affiliated Hospital, Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou, China; Institute of Life and Health Engineering (QYH), Jinan University, No. 601, West Huangpu Road, Guangzhou, China; State Key Laboratory of Oncology in South China (DX), Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou, China; and Department of Internal Medicine (DLY), James Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, U.S.A.
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  • Kou Peng,

    1. From the Departments of Neurology (LL, YL, YDW, ML, XDC, KP, XPL, YP) and Ultrasonography (YLW), The Second Affiliated Hospital, Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou, China; Institute of Life and Health Engineering (QYH), Jinan University, No. 601, West Huangpu Road, Guangzhou, China; State Key Laboratory of Oncology in South China (DX), Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou, China; and Department of Internal Medicine (DLY), James Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, U.S.A.
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  • Xiang Pen Li,

    1. From the Departments of Neurology (LL, YL, YDW, ML, XDC, KP, XPL, YP) and Ultrasonography (YLW), The Second Affiliated Hospital, Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou, China; Institute of Life and Health Engineering (QYH), Jinan University, No. 601, West Huangpu Road, Guangzhou, China; State Key Laboratory of Oncology in South China (DX), Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou, China; and Department of Internal Medicine (DLY), James Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, U.S.A.
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  • Dan Xie,

    1. From the Departments of Neurology (LL, YL, YDW, ML, XDC, KP, XPL, YP) and Ultrasonography (YLW), The Second Affiliated Hospital, Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou, China; Institute of Life and Health Engineering (QYH), Jinan University, No. 601, West Huangpu Road, Guangzhou, China; State Key Laboratory of Oncology in South China (DX), Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou, China; and Department of Internal Medicine (DLY), James Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, U.S.A.
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  • Yan Ling Wen,

    1. From the Departments of Neurology (LL, YL, YDW, ML, XDC, KP, XPL, YP) and Ultrasonography (YLW), The Second Affiliated Hospital, Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou, China; Institute of Life and Health Engineering (QYH), Jinan University, No. 601, West Huangpu Road, Guangzhou, China; State Key Laboratory of Oncology in South China (DX), Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou, China; and Department of Internal Medicine (DLY), James Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, U.S.A.
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  • De Ling Yin,

    1. From the Departments of Neurology (LL, YL, YDW, ML, XDC, KP, XPL, YP) and Ultrasonography (YLW), The Second Affiliated Hospital, Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou, China; Institute of Life and Health Engineering (QYH), Jinan University, No. 601, West Huangpu Road, Guangzhou, China; State Key Laboratory of Oncology in South China (DX), Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou, China; and Department of Internal Medicine (DLY), James Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, U.S.A.
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  • Ying Peng

    1. From the Departments of Neurology (LL, YL, YDW, ML, XDC, KP, XPL, YP) and Ultrasonography (YLW), The Second Affiliated Hospital, Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou, China; Institute of Life and Health Engineering (QYH), Jinan University, No. 601, West Huangpu Road, Guangzhou, China; State Key Laboratory of Oncology in South China (DX), Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou, China; and Department of Internal Medicine (DLY), James Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, U.S.A.
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Reprint requests: Ying Peng, MD, PhD, Professor and Director, Department of Neurology, The Second Affiliated Hospital, Sun Yat-Sen University, No. 107, West Yanjiang Road, Guangzhou 510120, China; Tel: 86-20-81332095; Fax: 86-20-81332833; E-mail: docpengy@yahoo.com.cn

Abstract

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.

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