[Cytotoxicity of troglitazone, structural analogue of alpha-tocopherol is mediated by inhibition of NAD(P)H:quinone oxidoreductase].
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.
Petrova
G V
GV
Donchenko
G V
GV
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000737:chemistry / Q000494:pharmacology*; D001728:Dicumarol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000737:chemistry / Q000494:pharmacology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D000077288:Troglitazone; D024502:alpha-Tocopherol / Q000737:chemistry / Q000494:pharmacology*
D002839:Chromans; D004791:Enzyme Inhibitors; D045162:Thiazolidinediones; D001728:Dicumarol; D016660:NAD(P)H Dehydrogenase (Quinone); D024502:alpha-Tocopherol; D000077288:Troglitazone