Antioxidant protection of phospholipid bilayers by alpha-tocopherol. Control of alpha-tocopherol status and lipid peroxidation by ascorbic acid and glutathione.

D C Liebler,D S Kling,D J Reed

doi:10.1016/s0021-9258(18)67210-2

Abstract

Factors affecting the balance between pro- and antioxidant effects of ascorbic acid and glutathione were studied in soybean phosphatidylcholine liposomes challenged with Fe2+/H2O2. Effective antioxidant protection by alpha-tocopherol appeared to be due to efficient reaction with lipid oxy-radicals in the bilayer rather than to interception of initiating oxygen radicals. At concentrations above a threshold level of approximately 0.2 mol % (based on phospholipid content), alpha-tocopherol completely suppressed lipid oxy-radical propagation, which was measured as malondialdehyde production. Both ascorbic acid and glutathione, alone or in combination, enhanced lipid oxy-radical propagation. Alpha-Tocopherol, incorporated into liposomes at concentrations above its threshold protective level, reversed the pro-oxidant effects of 0.1-1.0 mM ascorbic acid but not those of glutathione. Ascorbic acid also prevented alpha-tocopherol depletion. The combination of ascorbic acid and subthreshold levels of alpha-tocopherol only temporarily suppressed lipid oxy-radical propagation and did not maintain the alpha-tocopherol level. Glutathione antagonized the antioxidant action of the alpha-tocopherol/ascorbic acid combination regardless of alpha-tocopherol concentration. These observations indicate that membrane alpha-tocopherol status can control the balance between pro- and antioxidant effects of ascorbic acid. The data also provide the most direct evidence to date that ascorbic acid interacts directly with components of the phospholipid bilayer.

Highlights

Factors affecting the balance between pro- and an- esis that soluble cellular antioxidants, ascorbic tioxidant effects of ascorbic acid and glutathionweere acid, maintain membrane a-TH levels by regenerating a-TH studiedin soybean phosphatidylcholine liposomes chafrlo-m its oxidation products
Lenged with Fe2+/HzO2E. ffective antioxidant protec- T H semiquinone radical by ascorbic acid was reported to tion by a-tocopherol appeared to bedueto efficient proceed in homogenous solution with a bimolecular rate conreaction with lipid oxy-radicals in the bilayer rather than to interception of initiating oxygen radicals
Related studies indicate that the enonly temporarily suppressed lipid oxy-radical propa- zyme-mediated antioxidant action of GSH in rat liver microgation and did not maintain the a-tocopherol level. somes depends, at least in part, on the a-TH status of the Glutathione antagonized the antioxidant action of the membranes [26, 27]

Summary

Introduction

Factors affecting the balance between pro- and an- esis that soluble cellular antioxidants, ascorbic tioxidant effects of ascorbic acid and glutathionweere acid, maintain membrane a-TH levels by regenerating a-TH studiedin soybean phosphatidylcholine liposomes chafrlo-m its oxidation products. Ascorbic acid soluble antioxidants may exert pro-oxidant effects via prevented a-tocopherol depletion. Related studies indicate that the enonly temporarily suppressed lipid oxy-radical propa- zyme-mediated antioxidant action of GSH in rat liver microgation and did not maintain the a-tocopherol level.

Results

Conclusion