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20 avril 2011 3 20 /04 /avril /2011 11:42

J Neurosci Res. 2011 Apr 12. doi: 10.1002/jnr.22630. [Epub ahead of print]

Vitamin K has the potential to protect neurons from methylmercury-induced cell death In Vitro.

Sakaue MMori NOkazaki MKadowaki EKaneko THemmi NSekiguchi HMaki TOzawa AHara SArishima KYamamoto M.

Department of Anatomy II, School of Veterinary Medicine, Azabu University, Sagamihara, Japan; Department of Public Health and Molecular Toxicology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan. sakaue@azabu-u.ac.jp.

Vitamin K (VK) has a protective effect on neural cells.

Methylmercury is a neurotoxicant that directly induces neuronal death in vivo and in vitro.

Therefore, in the present study, we hypothesized that VK inhibits the neurotoxicity of methylmercury.

 

To prove our hypothesis in vitro, we investigated the protective effects of VKs (phylloquinone, vitamin K(1) ; menaquinone-4, vitamin K(2) ) on methylmercury-induced death in primary cultured neurons from the cerebella of rat pups.

As expected, VKs inhibited the death of the primary cultured neurons.

It has been reported that the mechanisms underlying methylmercury toxicity involve a decrement of intracellular glutathione (GSH).


Actually, treatment with GSH and a GSH inducer, N-acetyl cysteine, inhibited methylmercury-induced neuronal death in the present study.

 

Thus, we investigated whether VKs also have protective effects against GSH-depletion-induced cell death by employing two GSH reducers, L-buthionine sulfoximine (BSO) and diethyl maleate (DEM), in primary cultured neurons and human neuroblastoma IMR-32 cells.

 

Treatment with VKs affected BSO- and DEM-induced cell death in both cultures.

 

On the other hand, the intracellular GSH assay showed that VK(2) , menaquinone-4, did not restore the reduced GSH amount induced by methylmercury or BSO treatments.

 

These results indicate that VKs have the potential to protect neurons against the cytotoxicity of methylmercury and agents that deplete GSH, without increasing intracellular GSH levels.

 

The protective effect of VKs may lead to the development of treatments for neural diseases involving GSH depletion. 


PMID: 21488088 [PubMed - as supplied by publisher]

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