Toxic and Protective Effects of Antioxidants in Biomembranes
Natural and synthetic antioxidants (AOs) are widely used as stabilizers of biomembranes against lipid peroxidation (LPO). Natural AOs (tocopherols, ubiquinols) containing hydrocarbon “tails” do not disturb the membrane lipid bilayer. Synthetic AOs devoid of hydrocarbon radicals may perturb the lipid bilayer. It was shown that AOs devoid of hydrocarbon tails (butylated hydroxytoluene, 2,2,5,7,8-pentamethyl-6-hydroxychromane) exerted toxic effects on erythrocyte membranes (induced hemolysis), on sarcoplasmic reticulum membranes (inhibited Ca2+ -transport) and on platelet membranes (initiated Ca2+-dependent aggregation) in vitro. These AOs are the substrates of cytochrome P-450, and underwent oxidative hydroxylation. This suggests that they have short half-life times in biomembranes and in the organism. Antioxidants with hyrocarbon tails, are hydroxylated at very low rates and are slowly excreted. Antioxidants devoid of hydrocarbon tails, are 10–20 fold more potent LPO inhibitors than the corresponding AOs with hydrocarbon tails. The strategy of AOs application for long and short-term stabilization of biomembranes against LPO in vivo is discussed.
Key wordsAntioxidants Biomembranes Lipid peroxidation Cytochrome P-450
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- Burlakova E, Kuktina E, Khrapova N, Aristarkova S (1982 a) Interrelationship between the level of natural antioxidants and lipid oxidation in normal mouse liver and after injection of alpha-tocopherol. Biochemistry 47: 5: 822–827 (in Russian)Google Scholar
- Burlakova E, Kuktina E, Sarycheva I, Khrapova N, Aristarkova S (1982 b) Effect of lateral chain of tocopherols on oxidative reactions in the lipids. Biochemistry 47: 6: 987–993 (in Russian)Google Scholar
- Kagan V, Poliansky N, Muranov K, Shvedova A, Smirov L, Dynmaev K (1984) Inhibition of platelet aggregation and platelet phosphodiesterase of cyclic nucleotides by 3-hydroxypiridine derivatives. Bull Exp Biol Med 4: 416–418 (in Russian)Google Scholar
- Martonosi A (1968) Solubilization of microsomal adenosine triphosphatase. J Biol Chem 243: 1: 7181Google Scholar
- Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 239: 521–525Google Scholar
- Ritov VB, Komarov PG, Melgunov VP (1977) Ca’ -ATPase–an intrinsic protein in sacroplasmic reticulum membranes. Proc Acad Sci USSR 233,2: 204–208 (in Russian)Google Scholar
- Ullrich V, Weber P (1973) The 0-dealkylation of 7-ethoxycoumarin by liver microsomes: A direct fluorimetric test. Hoppe Seyler Z Physiol Chem 353: 514–520Google Scholar