EFFECTS OF BUTYLATED HYDROXYANISOLE AND DICOUMAROL ON THE TOXICITY OFMENADIONE TO RATS

The enzyme DT-diaphorase catalyses the 2-electron reduction of quinone s. This reaction may facilitate the detoxification of such compounds, since the hydroquinone so formed can be converted into non-toxic conju gates. There is evidence fbr the involvement of DT-diaphorase in the d etoxification of menadione (2-methyl-1,4-naphthoquinone) in a wide ran ge of cells and tissues in vitro, but no information is available on t he possible influence of this enzyme on the harmful effects of menadio ne 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 hydroxyan isole (BHA), a substance that increases the activity of this enzyme in vivo. They were then challenged with a toxic dose of menadione. Dicou marol increased the severity of menadione-induced haemolytic anaemia w hile BHA decreased it, consistent with a role for DT-diaphorase in the detoxification of menadione in vivo, as previously described in vitro . (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.