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Journal archive > 2009 > N 4 July-August

CYTOTOXICITY OF TROGLITAZONE, A STRUCTURAL ANALOGUE OF -TOCOPHEROL
IS MEDIATED BY INHIBITION OF NAD(P)H:QUINONE OXIDOREDUCTASE

G. V. Petrova, G. V. Donchenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
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It is established, that ?-tocopherol and pio­glitazone in concentration up to 100 µM did not change the rat thymocytes viability while troglitazone and ?-tocopherol with a short side chain up to 6 atoms of carbon (?-tocopherol C6) have the expressed cytotoxic effect. This is the first report demonstrating that troglitazone and ?-tocopherol C6, unlike ?-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 ?-tocopherol C6 is connected with the presence in their structure of chroman ring with a lateral chain modified in relation to ?-tocopherol and is mediated by inhibition of DT-diaphorase, a detoxifying enzyme of xenobiotics.

Key words: troglitazone, pioglitazone, ?-tocopherol, cytotoxicity, thymocytes.

The original article in Russian is available for download in PDF format.

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