title: The effects of ascorbate and alpha-tocopherol on the NADPH-dependent lipid peroxidation in human placental mitochondria.
abstract: The effects of ascorbate and alpha-tocopherol as antioxidants and as co-operative factors against NADPH-dependent lipid peroxidation in human placental mitochondria have been studied. The addition of ascorbate at low concentration (up to 50 microM) to the NADPH-generating system resulted in increasing lipid peroxidation and Fe3+ to Fe2+ reduction. High concentration of ascorbate (150 microM), which produced maximal rate of ascorbate-dependent lipid peroxidation, was found to inhibit almost completely NADPH-dependent lipid peroxidation by maintaining too much iron in its reduced form. Either stimulatory or inhibitory effect of ascorbate on NADPH-dependent lipid peroxidation depends on the appropriate Fe3+/Fe2+ ratio. Alpha-tocopherol caused a decrease of NADPH-dependent lipid peroxidation, inhibiting completely this process at 150 microM concentration. The inhibitory effect of alpha-tocopherol increased rapidly with the increasing ascorbate concentration, almost complete inhibition of NADPH-dependent lipid peroxidation being obtained at 25 microM alpha-tocopherol and 50 microM ascorbate. This strong inhibitory combined effect of alpha-tocopherol and ascorbate was independent of the Fe3+/Fe2+ ratio, as alpha-tocopherol is not able to reduce Fe3+ to Fe2+ under the conditions employed. These findings suggest that antioxidant effects of ascorbate in placental mitochondria are mediated by recycling of alpha-tocopherol rather than by strong reduction of Fe3+ to Fe2+. On the basis of the results obtained, we assume that adequate concentrations of alpha-tocopherol and ascorbate in placental tissue may prevent the release of lipid peroxide from placental mitochondria and therefore could be protective against the development of preeclampsia.
authors.affiliation: Department of Biochemistry, Medical University of Gdańsk, Faculty of Pharmacy, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Milczarek
authors.forename: J
authors.initials: J
authors.lastname: Klimek
authors.forename: L
authors.initials: L
authors.lastname: Zelewski
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008928:Mitochondria / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism* / Q000648:ultrastructure; D011247:Pregnancy; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D009249:NADP; D007501:Iron; D002374:Catalase; D001205:Ascorbic Acid