Abstract
The effects of dietary vitamin E deficiency on mouse cerebral membrane order and oxygen reactive species were studied. Quantitation of vitamin E levels in several brain regions showed greatest deficiencies in striatum and cerebellum, followed by substantia nigra, and cortex. Vitamin E deficiency increased central-core membrane order in cerebral P2 fraction, but was without effect in the superficial hydrophilic membrane domain. Oxygen radical formation was studied using the probe 2',7'-dichlorofluorescein diacetate. Basal generation rates of oxygen reactive species were 2.5-fold higher when compared to control animals. While hepatic levels of vitamin E are much more reduced than brain levels, in deficient mice, the rate of oxygen radical formation in the liver was unaltered. This implies an special susceptibility of the brain to deficiency of this lipophilic antioxidant vitamin. Data demonstrate that endogenous levels of free radical scavengers, such as vitamin E, may play an important role in maintaining basal oxygen radical levels and membrane integrity. The dietary vitamin E depletion paradigm suggests that a relation exists between elevated levels of oxygen radicals and more rigid hydrophobic central-cores in cerebral membranes, effects that may play a role in mechanisms underlying the neuropathologic lesions observed following vitamin E deficiency.
Highlights
Vit E plays in nerve tissue has been investigated by means of Vit E deficiency studies
Oxygen radical formation was determined by loading brain or liver homogenates (0.5% in 40mM Tris, pH 7.4) with 5μM DCFH-DA (Moleculur Probes, Eugene, OR) in methanol for I5 min at 37oC
It is possible that the brain may lack the compens.1tory properties to adapt to oxidative radical fluxes as effectively as 1he liver. These data demon!>trate that the gener.11ion of oxygen radicals by the brain is regulated by endogenous antioxidants, such as Vit E. which appear to be responsible for 01.1intaining both :t homeostatic oxidative status, and physiologic:illy effective membrane order
Summary
Community & Environmental Medicine, Southern Occupational Health Center, University ofDlifomia Irvine, CA 92717. Summary: The effects of dietary vitamin E deficiency on mouse cerebral membrane order and oxygen r(active species were studied. Funhcnnore, 10 our knowledge no studies exist regarding the effects of Vit E deficiency on antioxidant and membrnne order parameters in neural tissue, oxygen radic:1ls are thought to play a major role in events lc:iding to biologic~1l membrane damage (for review sec 17). The present study investig:ites the effects of Vit E deficiency on cerebral oxygen radical formation, using DCFH-DA. Oxygen radical formation was determined by loading brain or liver homogenates (0.5% in 40mM Tris, pH 7.4) with 5μM DCFH-DA (Moleculur Probes, Eugene, OR) in methanol for I5 min at 37oC. The accepted level of significance was p
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