Effects of dicoumarol on cytotoxicity caused by tert-butylhydroquinone in isolated rat hepatocytes.
The effects of dicoumarol, an inhibitor of DT-diaphorase, on the cytotoxicity of tert-butylhydroquinone (tBHQ) were studied in freshly isolated rat hepatocytes. Addition of tBHQ (0.5 mM) to hepatocytes resulted in a time-dependent cell death accompanied by depletion of intracellular ATP, glutathione (GSH), and protein thiols. Pretreatment of hepatocytes with dicoumarol (30 microM) did not affect cell viability or cellular levels of ATP, GSH, or protein thiols during the incubation period; however, dicoumarol did promote the appearance of cell blebs and the depletion of ATP and protein thiols induced by tBHQ and ultimately enhanced the cytotoxicity of tBHQ.
Nakagawa
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Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D001728:Dicumarol / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006873:Hydroquinones / Q000633:toxicity*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors*; D051381:Rats; D011916:Rats, Inbred F344
D000975:Antioxidants; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D001728:Dicumarol; D000255:Adenosine Triphosphate; C018855:2-tert-butylhydroquinone; D016660:NAD(P)H Dehydrogenase (Quinone); D005978:Glutathione