Phenobarbital-induced cytoprotective mechanisms in menadione metabolism: the role of glutathione reductase and DT-diaphorase.
1. Treatment with N,N-bis (2-chloroethyl)-N-nitrosourea (BCNU) (80 microM) led to decreases in cell viability in both naive and sodium phenobarbital (PB) induced hepatocytes. 2. Dicumarol (30 microM) selectively increased the cytotoxicity of menadione in hepatocytes isolated from naive vs PB-pretreated rats. 3. Inclusion of both BCNU and dicumarol to the incubation medium abolished the characteristic concentration-response curves of the hepatocytes for menadione. 4. A greater proportion of menadione was metabolized by DT-diaphorase in the hepatocytes isolated from PB-pretreated rats. 5. The role of glutathione reductase vs DT-diaphorase in mitigating menadione-cytotoxicity in the naive vs PB-induced hepatocyte is discussed.
Utley
W S
WS
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
Mehendale
H M
HM
D000818:Animals; D002330:Carmustine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D001728:Dicumarol / Q000494:pharmacology; D004347:Drug Interactions; D005980:Glutathione Reductase / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone); D010634:Phenobarbital / Q000494:pharmacology*; D011808:Quinone Reductases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism; D014812:Vitamin K / Q000378:metabolism* / Q000494:pharmacology
D013481:Superoxides; D014812:Vitamin K; D001728:Dicumarol; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D005980:Glutathione Reductase; D002330:Carmustine; D010634:Phenobarbital