1 / 28

Antioxidants and Fetal Protection Against Ethanol Teratogenicity. Review of Experimental Data

Antioxidants and Fetal Protection Against Ethanol Teratogenicity. Review of Experimental Data. Raanan Cohen-Kerem Gideon Koren. Outline. Introduction Alcohol as an oxidant Studies review Cell culture Animal models Conclusions . Introduction.

mitch
Télécharger la présentation

Antioxidants and Fetal Protection Against Ethanol Teratogenicity. Review of Experimental Data

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Antioxidants and Fetal Protection Against Ethanol Teratogenicity.Review of Experimental Data Raanan Cohen-Kerem Gideon Koren FACE, Sep 2002

  2. Outline • Introduction • Alcohol as an oxidant • Studies review • Cell culture • Animal models • Conclusions FACE, Sep 2002

  3. Introduction • Heavy drinking during pregnancy can result in serious adverse outcomes for the fetus • Fetal Alcohol Syndrome (FAS) • pre and/or postnatal growth retardation • central nervous system damage • typical facial dysmorphology • Incidence of FAS -0.97/1000 a year • 50% of women in childbearing age consume alcohol FACE, Sep 2002

  4. Introduction • The fetus is more susceptible to ethanol than the mother • Ethanol affects biochemical processes and cellular structures through various mechanisms and most of them are still far from being completely understood FACE, Sep 2002

  5. Mechanisms of ethanol induced damage • Amino acid activated ion channels NMDA GABA • Hypoxia • FAEE • Retinoic acid • L1 neural cell adhesion molecule • Endocrine • Oxidative stress FACE, Sep 2002

  6. Objective • To review the data of antioxidant effects in experimental models of fetal alcohol syndrome Treatment with antioxidants in pregnant alcoholic women may potentially prevent ethanol teratogenicity FACE, Sep 2002

  7. CH3-CH-OH (Hydroxyethyl) Direct + - Indirect - How does oxidative stress occur? Peroxidation of lipids, nucleic acids, and proteins + Reactive oxygen species (ROS) + + OH (Hydroxyl) CYP2E1 + Mitochondrial Damage C2H5.OH (Ethanol) Mitochondria Glutathione pool Glutathione peroxidase activity FACE, Sep 2002

  8. Antioxidants • Endogenous • superoxide dismutase • glutathione peroxidase • catalase • Exogenous • Vitamins Vitamin C Tocopherols b-Carotene Folic acid FACE, Sep 2002

  9. Literature Search • Databases: • MEDLINE • EMBASE • Keywords: pregnancy, ethanol, fetus, antioxidants, animal • Included were reports on pregnancy outcome of cell culture or animal FAS model supplemented with antioxidants FACE, Sep 2002

  10. In the lab FACE, Sep 2002

  11. Vitamin E and beta-carotene protect against ethanol combined with ischemia in an embryonic rat hippocampal culture model of FAS Mitchell, Neurosci Lett 263:1999 ; Alcohol 17:1999. • Reduced levels of cytochrome c oxidase mRNA Kim et al, 2001 • Dose-dependent decreased viability of hippocampal cell cultures FACE, Sep 2002

  12. Vitamin E and beta-carotene protect against ethanol combined with ischemia in an embryonic rat hippocampal culture model of FAS Mitchell, Neurosci Lett 263:1999 ; Alcohol 17:1999. • Nutritional supplementation • Vitamin E • b-Carotene • Limitations • Oxidative stress measures • Cells were exposed to ethanol in culture but not in vivo FACE, Sep 2002

  13. Effect of ethanol on rat fetal hepatocytes: studies on cell replication, lipid peroxidation and glutathione Devi, Hepatology18:1993 • 2.0mg/ml ethanol (~1/10 of Mitchell’s study) • Outcome measure: cell replication • Glutathione • Antioxidants: • N-acetylcysteine • S-adenosylmethionine • Vitamin E FACE, Sep 2002

  14. In the lab FACE, Sep 2002

  15. FAS in rats: conditions for improvement of ethanol effects on fetal cerebral development with supplementary agents Tanaka,Biol Neonate 54:1988. • Pregnant rats were fed 20% ethanol +0.03% vit. E, or 10% ethanol + 0.02% vit. E • Outcome measures: • body • cerebral weights • The investigation failed to show protective effect of vit. E FACE, Sep 2002

  16. Protective effects of the flavonoid mixture, silymarin, on fetal rat brain and liver La Grange, J Ethnopharmacol 65:1999. • Antioxidant: Flavonoids (sylibum marianum) • Silymarin-Phytosome • Outcome measure • Tissue GGT activity in embryonic liver and brain FACE, Sep 2002

  17. Protective effects of the flavonoid mixture, silymarin, on fetal rat brain and liver La Grange, J Ethnopharmacol 65:1999. • Limitation • No oxidative stress measures to correlate FACE, Sep 2002

  18. Fetoprotectivity of the flavanolignan compound siliphosagainst ethanol-induced toxicity Edwards, Phytother Res 14 :2000. • Antioxidant: Sylibin • Outcome measures • Fetal survival • GGT activity in the embryonic brain and liver • Glutathione (GSH) activity in the embryonic brain and liver FACE, Sep 2002

  19. Prevention by a silymarin/phospholipid compound of ethanol-induced social learning deficits in rats Reid, Planta Med 65:1999. • Antioxidant: Silymarin • Outcome measure • social recognition score of the offspring was obtained in two periods of 5 minutes separated by 60 minutes interval • Limitations • No oxidative stress measures to correlate FACE, Sep 2002

  20. Fetal Body Weight Protective effect of folic acid against oxidative stress produced in 21- day postpartum rats by maternal-ethanol chronic consumption during pregnancy and lactation period Cano, Free Radic Res34:2001. • Antioxidant: Folic acid 152mg/day • Outcome measures • Body weight • Glutathione reductase in the fetal liver & pancreas • Carbonyl group proteins FACE, Sep 2002

  21. Protective effect of folic acid against oxidative stress produced in 21- day postpartum rats by maternal-ethanol chronic consumption during pregnancy and lactation period Cano, Free Radic Res34:2001. Fetal glutathione reductase *-ethanol vs. control and vs.ethanol+FA Fetal carbonyl groups FACE, Sep 2002

  22. FACE, Sep 2002

  23. Alpha-tocopherol and gamma-tocopherol attenuate ethanol-induced changes in membrane fatty acid composition in embryonic chick brains Miller, Teratology 62 :2000. • Injection of ethanol with or without vitamin E • Outcome measure: • long chain membrane fatty acids in brain tissue • Brain mass FACE, Sep 2002

  24. Alpha-tocopherol and gamma-tocopherol attenuate ethanol-induced changes in membrane fatty acid composition in embryonic chick brains Miller, Teratology 62 :2000. • Reduction in stearic acid, oleic acid, linoleic acid, linolenic acid and arachidonic acid • Reduction in brain mass • Supplementation of vitamin E prevented these effects and maintained brain mass FACE, Sep 2002

  25. Discussion • A protective effect of antioxidants against ethanol-induced damage is observed in the available animal studies • Can we apply this prophylactic treatment to pregnant women? FACE, Sep 2002

  26. Lancet 1999; 354: 810-16 Discussion • Applying antioxidant treatment in pregnancy is not a new concept • Antioxidants (Vitamins E & C) for pre-eclampsia • These antioxidants were not found to be teratogenic FACE, Sep 2002

  27. Conclusions • Oxidative stress is a principal mechanism of ethanol induced damage • Ethanol induced fetotoxicity was shown to be reduced by antioxidants in cell cultures and animal models • Data regarding these effects in human are not available yet FACE, Sep 2002

  28. Take home message • Treating women who abuse alcohol during pregnancy with antioxidants by food supplements as vitamins is appealing: • It may hold a protective effect against FAS as shown in the reviewed studies • it may reverse other nutritional deficits common in this population FACE, Sep 2002

More Related