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Ukrains'kyi biokhimichnyi zhurnal (1999 )

[Cytotoxicity of troglitazone, structural analogue of alpha-tocopherol is mediated by inhibition of NAD(P)H:quinone oxidoreductase].


PMID 20387640

Abstract

It is established, that alpha-tocopherol and pioglitazone in concentration up to 100 microM did not change the rat thymocytes viability while troglitazone and alpha-tocopherol with a short side chain up to 6 atoms of carbon (alpha-tocopherol C6) have the expressed cytotoxic effect. This is the first report demonstrating that troglitazone and alpha-tocopherol C6, unlike a-tocopherol and pioglitazone substantially inhibited the activity of NAD(P)H:quinone oxidoreductase (DT-diaphorase) and this effect is increased with specific DT-diaphorase inhibitor, dicoumarol. Based on these observations, we generalize that cytotoxic action of troglitazone and alpha-tocopherol C6 is connected with the presence in their structure of chroman ring with a lateral chain modified in relation to alpha-tocopherol and is mediated by inhibition of DT-diaphorase, a detoxifying enzyme of xenobiotics.

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