Suppression of neuro-inflammatory signaling cascade by tocotrienol can prevent chronic alcohol-induced cognitive dysfunction in rats.

Abstract

Chronic alcohol intake is known to induce the selective neuronal damage associated with increase oxidative-nitrosative stress and activation of inflammatory cascade finally resulting in neuronal apoptosis and thus dementia. In the present study, we investigated the comparative effect of both the isoforms of vitamin E, alpha-tocopherol and tocotrienol against chronic alcohol-induced cognitive dysfunction in rats. Male Wistar rats were given ethanol (10g/kg; oral gavage) for 10 weeks, and treated with alpha-tocopherol and tocotrienol for the same duration. The learning and memory behavior was assessed using Morris water maze and elevated plus maze test. The rats were sacrificed at the end of 10th week and cytoplasmic fractions of cerebral cortex and hippocampus were prepared for the quantification of acetylcholinesterase activity, oxidative-nitrosative stress parameters, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta). From the 6th week onwards, ethanol-treated rats showed significant increase in transfer latency in both the behavioral paradigms which was coupled with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, TNF-alpha and IL-1beta levels in different brain regions of ethanol-treated rats. Co-administration of alpha-tocopherol as well as tocotrienol significantly and dose-dependently prevented these behavioral, biochemical and molecular changes in the brains of ethanol-treated rats. However, the effects were more pronounced with tocotrienol. The current study thus demonstrates the possible involvement of oxidative-nitrosative stress mediated activation of inflammatory cascade in chronic alcohol-induced cognitive dysfunction and also suggests the effectiveness of vitamin E isoforms, of which tocotrienol being more potent, in preventing the cognitive deficits associated with chronic alcohol consumption.

• Authors: Vinod Tiwari, Anurag Kuhad, Kanwaljit Chopra
• Journal: Behavioural brain research (Behav Brain Res) Vol. 203 Issue 2 Pg. 296-303 (Nov 05 2009) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 19464322 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1beta
• Nitrites
• Tocotrienols
• Tumor Necrosis Factor-alpha
• Acetylcholinesterase
• alpha-Tocopherol

Topics

• Acetylcholinesterase (metabolism)
• Alcohol Amnestic Disorder (drug therapy, metabolism)
• Animals
• Cerebral Cortex (drug effects, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Hippocampus (drug effects, metabolism)
• Interleukin-1beta (metabolism)
• Lipid Peroxidation (drug effects)
• Male
• Maze Learning
• Memory
• Motor Activity
• Nitrites (metabolism)
• Oxidative Stress (drug effects)
• Rats
• Rats, Wistar
• Tocotrienols (therapeutic use)
• Tumor Necrosis Factor-alpha (metabolism)
• alpha-Tocopherol (therapeutic use)