Effects of butylated hydroxyanisole and dicoumarol on the toxicity of menadione to rats.
The enzyme DT-diaphorase catalyses the 2-electron reduction of quinones. This reaction may facilitate the detoxification of such compounds, since the hydroquinone so formed can be converted into non-toxic conjugates. There is evidence for the involvement of DT-diaphorase in the detoxification of menadione (2-methyl-1,4-naphthoquinone) in a wide range of cells and tissues in vitro, but no information is available on the possible influence of this enzyme on the harmful effects of menadione in vivo. In animals, menadione is selectively toxic to erythrocytes, causing haemolytic anaemia. In the present study, rats were treated with dicoumarol, an inhibitor of DT-diaphorase, or butylated hydroxyanisole (BHA), a substance that increases the activity of this enzyme in vivo. They were then challenged with a toxic dose of menadione. Dicoumarol increased the severity of menadione-induced haemolytic anaemia while BHA decreased it, consistent with a role for DT-diaphorase in the detoxification of menadione in vivo, as previously described in vitro.
Munday
R
R
AgResearch, Ruakura Agricultural Research Centre, Hamilton, New Zealand. mundayr@agresearch.cri.nz
Smith
B L
BL
Munday
C M
CM
D000743:Anemia, Hemolytic / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D001728:Dicumarol / Q000494:pharmacology*; D008058:Dihydrolipoamide Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006366:Heinz Bodies / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006490:Hemostatics / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D014812:Vitamin K / Q000633:toxicity*
D000975:Antioxidants; D004791:Enzyme Inhibitors; D006490:Hemostatics; D014812:Vitamin K; D002083:Butylated Hydroxyanisole; D001728:Dicumarol; D016660:NAD(P)H Dehydrogenase (Quinone); D008058:Dihydrolipoamide Dehydrogenase