Neuroprotective Effects of α-Tocotrienol on Kainic Acid-Induced Neurotoxicity in Organotypic Hippocampal Slice Cultures

Abstract

Vitamin E, such as alpha-tocopherol (ATPH) and alpha-tocotrienol (ATTN), is a chain-breaking antioxidant that prevents the chain propagation step during lipid peroxidation. In the present study, we investigated the effects of ATTN on KA-induced neuronal death using organotypic hippocampal slice culture (OHSC) and compared the neuroprotective effects of ATTN and ATPH. After 15 h KA (5 μM) treatment, delayed neuronal death was detected in the CA3 region and reactive oxygen species (ROS) formation and lipid peroxidation were also increased. Both co-treatment and post-treatment of ATPH (100 μM) or ATTN (100 μM) significantly increased the cell survival and reduced the number of TUNEL-positive cells in the CA3 region. Increased dichlorofluorescein (DCF) fluorescence and levels of thiobarbiturate reactive substances (TBARS) were decreased by ATPH and ATTN treatment. These data suggest that ATPH and ATTN treatment have protective effects on KA-induced cell death in OHSC. ATTN treatment tended to be more effective than ATPH treatment, even though there was no significant difference between ATPH and ATTN in co-treatment or post-treatment.

Neuroprotective Effect of Antioxidants in the Brain

“…Therapeutic effects of α-tocopherol by application of vitamin E in neurological lesions caused by neuronal excitotoxicity and the conditional activation of neuroglial cells have also been reported. In KA treatment-induced oxidative stress [ 166 ], delayed neuronal death was detected in the hippocampal CA3 region and ROS formation and lipid peroxidation were also increased. Both co-treatment and post-treatment with α-tocopherol (100 µM) or α-tocotrienol (100 µM) significantly increased cell survival and reduced the number of TUNEL-positive cells in the CA3 region.…”

Effects of Aging and Tocotrienol‐Rich Fraction Supplementation on Brain Arginine Metabolism in Rats

“…Moreover, cell culture studies have demonstrated the neuroprotective effects of vitamin E, with tocotrienol being more potent than tocopherol [ 27 – 29 ]. The mechanisms of action of tocotrienol includes but not limited to free radical scavenging and modulation of arachidonic acid metabolism [ 28 , 30 – 32 ], kainic acid metabolism [ 33 ], homocysteic acid metabolism [ 34 ], and mitochondrial metabolism [ 35 ].…”

Carbofuran Induced Oxidative Stress Mediated Alterations in Na+‐K+‐ATPase Activity in Rat Brain: Amelioration by Vitamin E

“…Vitamin C serves as aqueous phase antioxidant and its antioxidant potential is reported against carbofuran‐induced oxidative stress in rat brain and erythrocytes . Vitamin E, a group of tocopherols and tocotrienols existing in alpha, beta, gamma, and delta forms, is an important component of biological membrane having both antioxidant and nonantioxidant functions . α‐Tocopherol and α‐tocotrienol forms of vitamin E exhibit highest biological activity .…”

“…Vitamin E, a group of tocopherols and tocotrienols existing in alpha, beta, gamma, and delta forms, is an important component of biological membrane having both antioxidant and nonantioxidant functions . α‐Tocopherol and α‐tocotrienol forms of vitamin E exhibit highest biological activity . Vitamin E protects biomolecules by scavenging lipid peroxyl radicals and terminating the lipid peroxidation chain reaction .…”