alpha-Tocopherol depletion eliminates the regional differences in adrenal mitochondrial lipid peroxidation

Prior studies demonstrated far greater amounts of lipid peroxidation (LP) in mitochondria from the zona reticularis (inner zone) of the guinea pig adrenal cortex than in mitochondria from the outer zone (zona fasciculata + zona glomerulosa) of the gland. alpha-Tocopherol concentrations, by contrast, were greater in the outer zone. To determine if the differences in alpha-tocopherol content were responsible for the regional differences in LP, the effects of alpha-tocopherol deficiency on mitochondrial LP were investigated. Tocopherol deficiency had relatively little effect on ferrous ion- or ascorbic acid-induced LP in inner zone mitochondria. However, depletion of adrenal tocopherol substantially increased outer zone LP, eliminating the differences between the two zones. Fatty acid analyses revealed that mitochondria from tocopherol-deficient animals contained significantly less linoleic acid (C18:2) and arachidonic acid (C20:4) than those from controls, suggesting peroxidative losses in vivo. In mitochondria from control animals, subphysiological concentrations of ascorbic acid stimulated LP, but physiological levels did not. However, in tocopherol-depleted mitochondria, even physiological concentrations of ascorbic acid stimulated LP. The results indicate that the intra-adrenal distribution of alpha-tocopherol is responsible for the regional differences in mitochondrial LP and that alpha-tocopherol is a major determinant of ascorbic acid actions on adrenal LP. The data also provide evidence of adrenal LP in vivo in tocopherol-deficient animals.