Effects of vitamin E supplementation on plasma membrane permeabilization and fluidization induced by chlorpromazine in the rat brain

Abstract

Neurotransmitter receptors play a key role in most research on antipsychotic drugs, but little is known about the effects of these drugs on the plasma membrane in the central nervous system. Therefore, we investigated whether chlorpromazine (CPZ), a typical phenothiazine antipsychotic drug, affects the plasma membrane integrity in the rat brain, and if so, whether these membrane alterations can be prevented by dietary supplementation with vitamin E, which has been shown to be an antioxidant and also a membrane-stabilizer. Leakage of [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG)-6-phosphate from rat striatal slices and decrease in 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy were used as indexes for plasma membrane permeabilization and fluidization, respectively. CPZ induced leakage of [(18)F]FDG-6-phosphate from striatal slices, and the leakage was delayed in the vitamin E-supplemented group compared to that in the normal diet group. The decrease in plasma membrane anisotropy induced by CPZ was significantly attenuated by vitamin E supplementation. Chronic treatment with alpha-phenyl-N-tert-butyl nitrone, a free radical scavenger, had no effect on CPZ-induced plasma membrane permeabilization, and the treatment with CPZ did not induce lipid peroxidation. CPZ can reduce plasma membrane integrity in the brain, and this reduction can be prevented by vitamin E via its membrane-stabilizing properties, not via its antioxidant activity.

Interplay between Structure and Fluidity of Model Lipid Membranes under Oxidative Attack

“…l -ascorbic acid (vitamin C) and α-tocopherol (vitamin E) are generally regarded as protecting lipid membranes from the injurious effect of ROS, , but specific questions, such as whether both vitamins employ the same protective mechanism, remain largely unanswered. Vitamin C acts as a scavenger of ROS through antioxidation, whereas vitamin E bound to membranes acts as a stabilizer to maintain the integrity of membranes beyond its function as an antioxidant. , Elucidation of the mechanism that underlies the inhibition of altered membrane fluidity is important for the development of effective therapies against cellular oxidative injury.…”

“…Vitamin C acts as a scavenger of ROS through antioxidation, whereas vitamin E bound to membranes acts as a stabilizer to maintain the integrity of membranes beyond its function as an antioxidant. 24,25 Elucidation of the mechanism that underlies the inhibition of altered membrane fluidity is important for the development of effective therapies against cellular oxidative injury.…”

Distribution of Tocopherols and Tocotrienols in Guinea Pig Tissues Following Parenteral Lipid Emulsion Infusion

“…Vitamin E is the primary lipid‐soluble antioxidant in the human body 1 . The structure of vitamin E, with its hydrophobic side chain, makes it unique and indispensable in protecting cell membranes from oxidant damage 38 , 39 . Due to its preferential accumulation in the body, α‐tocopherol arguably is the most important vitamin E homolog believed to modify the course of many oxidative diseases 40 , 41 …”

Tocopherol and tocotrienol homologs in parenteral lipid emulsions

“…Vitamin E is the primary fat‐soluble antioxidant in the human body . The structure of vitamin E, with its hydrophobic side chain, makes it unique and indispensable in protecting cell membranes from oxidant damage . Due to its preferential accumulation in the body, α‐tocopherol arguably is the most important vitamin E homolog believed to modify the course of many oxidative diseases that include cardiovascular disease .…”