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Prophylactic Effects of Levamisole and Vitamin E on Phenobarbital-induced Cleft Palate and Spina Bifida in Rat Embryos

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      Abstract

      There are many reports that show the teratogenic effects of phenobarbital can be decreased by stimulation of maternal immune system. Therefore, in this study, the prophylactic effects of levamisole and vitamin E on teratogenic effects of phenobarbital were compared. This study was performed on 20 pregnant rats that were divided into four groups. Control group received normal saline and test groups received phenobarbital (120 mg/kg), phenobarbital (120 mg/kg) plus levamisole (10 mg/kg) and phenobarbital (120 mg/kg) plus vitamin E (100 mg/kg) intraperitoneally at 9-11th days of gestation, respectively. Fetuses were collected at 20th day of gestation and after determination of weight and length; they were stained by Alizarin red - Alcian blue method. Cleft palate and spina bifida incidence were 66.66% and 69.44% in fetuses of rats that had received only phenobarbital. Cleft palate and spina bifida incidence were 65.45% and 38.18% had in the group which had received phenobarbital plus levamisole. However, Cleft palate and spina bifida incidence were 54.54% and 27.27% in the group which had received phenobarbital plus vitamin E. The arithmetic means of the weight and length of fetuses the rats that had received levamisole and vitamin E were significantly greater than that of those that had received only phenobarbital. Vitamin E had a greater prophylactic effect than levamisole on the incidence of phenobarbital-induced cleft palate and spina bifida. However, the difference was not significant.

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      The Pharmacological Basis of Therapeutics

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        Antioxidants and fetal protection against ethanol teratogenicity. I. Review of the experimental data and implications to humans.

        Ethanol is the most common human teratogen, and heavy drinking during pregnancy can result in serious adverse outcomes to the fetus. The cellular mechanisms by which ethanol induces damage in utero are not well understood, while induction of oxidative stress is believed to be one putative mechanism. Our objective is to review the data of antioxidant effects in experimental models of fetal alcohol syndrome. Prior to the description of the available experimental data, we will briefly review the mechanisms leading to ethanol-induced oxidative stress. Ethanol-induced oxidative damage to the fetus could be attenuated by a variety of antioxidants as was documented in whole animal and tissue culture studies. Experiments, retrieved from the literature search, are described and criticized. Although experimental data are still limited, the application of a treatment strategy that includes antioxidants is justified since antioxidant treatment in human pregnancy for pre-eclampsia was demonstrated to be safe and effective. The available experimental evidence and the safety of vitamins C and E in pregnancy suggest that experimental use of antioxidants in alcohol-consuming mothers should be seriously considered to reduce fetal alcohol damage.
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          Pregnancy outcome following high doses of Vitamin E supplementation.

          The recommended dose of Vitamin E in human pregnancy is 22-30 mg/day. High doses of Vitamin E (>or=400 IU/day) have been shown to attenuate or even prevent the damaging effect of ethanol and diabetes on the fetus in experimental animal models. The Motherisk program prospectively enrolled, and followed-up on, 82 pregnant women exposed to high doses (>or=400 IU/day) of Vitamin E during the first trimester of pregnancy. Pregnancy outcome was compared to a matched control group. The study group (n=82) was exposed to Vitamin E at doses ranging from 400-1200 IU/day. There was one pregnancy with major malformation (omphalocele) in study group. There was an apparent decrease in mean birth weight (3173+/-467 g) in Vitamin E group as compare to control (3417+/-565 g; P=0.0015); however, there were no significant differences in rates of live births, preterm deliveries, miscarriages and stillbirths. Therefore, it is concluded that consumption of high doses of Vitamin E during the first trimester of pregnancy does not appear to be associated with an increased risk for major malformations, but may be associated with decrease in birth weight.
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            Author and article information

            Affiliations
            [a ] Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Shahid Chamran University, Ahwaz, Iran.
            [b ] Department of Pharmacology, Faculty of Veterinary Medicine, Shahid Chamran University, Ahwaz, Iran.
            Author notes
            [* ]Corresponding author: E-mail: mkhaksarymahabady@yahoo.com
            Journal
            Iran J Pharm Res
            Iran J Pharm Res
            IJPR
            Iranian Journal of Pharmaceutical Research : IJPR
            Shaheed Beheshti University of Medical Sciences (Tehran, Iran )
            1735-0328
            1726-6890
            Winter 2011
            : 10
            : 1
            : 135-140
            24363692
            3869582
            ijpr-10-135
            © 2011 by School of Pharmacy, Shaheed Beheshti University of Medical Sciences and Health Services

            This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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