Tocotrienol ameliorates behavioral and biochemical alterations in the rat model of alcoholic neuropathy

Tiwari V, Kuhad A, Chopra K. Source

Pain. 2009 Sep;145(1-2):129-35. Epub 2009 Jun 21

Chronic alcohol consumption produces a painful peripheral neuropathy for which there is no reliable successful therapy, which is mainly due to lack of understanding of its pathobiology. Alcoholic neuropathy is characterized by spontaneous burning pain, hyperalgesia (an exaggerated pain in response to painful stimuli) and allodynia (a pain evoked by normally innocuous stimuli). Chronic alcohol intake is known to decrease the nociceptive threshold with increased oxidative-nitrosative stress and release of proinflammatory cytokines coupled with activation of protein kinase C. The aim of the present study is to investigate the effect of both isoforms of vitamin E, alpha-tocopherol (100mg/kg; oral gavage) and tocotrienol (50, 100 and 200mg/kg; oral gavage) against alcohol-induced neuropathic pain in rats. Male Wistar rats, were administered 35% v/v ethanol (10 g/kg; oral gavage) for 10 weeks, and were treated with alpha-tocopherol and tocotrienol for the same duration. Ethanol-treated animals showed a significant decrease in nociceptive threshold as evident from decreased tail flick latency (thermal hyperalgesia) and decreased paw-withdrawal threshold in Randall-Sellito test (mechanical hyperalgesia) and von-Frey hair test (mechanical allodynia) along with the reduction in nerve glutathione and superoxide dismutase levels. TNF-alpha and IL-1beta levels were also significantly increased in both serum and sciatic nerve of ethanol-treated rats. Treatment with alpha-tocopherol and tocotrienol for 10 weeks significantly improved all the above-stated functional and biochemical deficits in a dose-dependent manner with more potent effects observed with tocotrienol. The study demonstrates the effectiveness of tocotrienol in attenuation of alcoholic neuropathy.

Tocotrienols suppress proinflammatory markers and cyclooxygenase-2 expression in RAW264.7 macrophages

Yam ML, Abdul Hafid SR, Cheng HM, Nesaretnam K.

Lipids. 2009 Sep;44(9):787-97. Epub 2009 Aug 5.

Tocotrienols are powerful chain breaking antioxidant. Moreover, they are now known to exhibit various non-antioxidant properties such as anti-cancer, neuroprotective and hypocholesterolemic functions. This study was undertaken to investigate the anti-inflammatory effects of tocotrienol-rich fraction (TRF) and individual tocotrienol isoforms namely delta-, gamma-, and alpha-tocotrienol on lipopolysaccharide-stimulated RAW264.7 macrophages. The widely studied vitamin E form, alpha-tocopherol, was used as comparison. Stimulation of RAW264.7 with lipopolysaccharide induced the release of various inflammatory markers. 10 mcirog/ml of TRF and all tocotrienol isoforms significantly inhibited the production of interleukin-6 and nitric oxide. However, only alpha-tocotrienol demonstrated a significant effect in lowering tumor necrosis factor-alpha production. Besides, TRF and all tocotrienol isoforms except gamma-tocotrienol reduced prostaglandin E(2) release. It was accompanied by the down-regulation of cyclooxygenase-2 gene expression by all vitamin E forms except alpha-tocopherol. Collectively, the data suggested that tocotrienols are better anti-inflammatory agents than alpha-tocopherol and the most effective form is delta-tocotrienol.

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