Study Title:
Protection of cerebellar
granule cells by tocopherols and tocotrienols against
methylmercury toxicity.
Study Abstract:
Excessive free radical
formation has been implicated as one of the causative
factors in neurotoxic damage associated with variety of
metals, including methylmercury (MeHg). Although the
mechanisms associated with MeHg-dependent neurotoxicity
remains are unclear, it is known that MeHg leads to
neurotoxicity in cerebellar granule cells (CGCs). In vitro
exposure of murine CGC primary cultures to MeHg resulted
in time- and concentration-dependent cell death. The
present study was designed to assess the effect of
fat-soluble antioxidant tocopherols and tocotrienols
(unsaturated vitamin E) on MeHg-induced neurotoxicity
using cultured CGCs. Significant protection from MeHg-induced
neuronal cell death was observed with both tocopherols and
tocotrienols. Moreover, we observed that tocotrienols are
multi-fold more potent than tocopherols in protecting CGCs
against MeHg neurotoxicity. At micromolar concentration,
tocotrienols, but not tocopherols, showed complete
protection by an antioxidant mechanism. Similarly,
tocopherols and tocotrienols showed a protective effect on
CGCs migration against MeHg-toxicity. These results
suggested that oxidative events may contribute to MeHg
toxicity in isolated cerebellar granule neurons, and that
tocotrienols are potent supplements for pharmacological
protection of the developing brain exposed to MeHg.
Study Information:
Shichiri M,
Takanezawa Y, Uchida K, Tamai H, Arai H. Protection of
cerebellar granule cells by tocopherols and tocotrienols
against methylmercury toxicity. Brain Res. 2007 November
1182:106-15.
Department of Health Chemistry, Graduate School of
Pharmaceutical Sciences, The University of Tokyo, 7-3-1,
Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
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