CAPACITY OF RAT-BRAIN TO METABOLIZE M-DINITROBENZENE - AN IN-VITRO STUDY

m-dinitrobenzene (m-DNB) is a neurotoxin producing selective brain les ions, but the in situ metabolic fate of m-DNB in brain is unknown. In this study nitroreductive capacity of brain towards m-dinitrobenzene ( m-DNB) has been investigated. Tissue slices from F344 rat brain stem, forebrain, and liver were separately incubated with 0.2 mM m-DNB. m-DN B and its metabolites were detected by HPLC, and identified by either HPLC or Mass Spectrometry (MS). All three types of tissues showed meta bolic activity towards m-DNB. Metabolic disposal of m-DNB was 1.05+/-0 .11 mu mol/g wet weight/h in liver, 0.49+/-0.05 in brain stem, and 0.4 4+/-0.05 in forebrain (mean+/-SD, n=4). m-Nitroaniline was found to be the main metabolite produced by both brain and liver slices, represen ting 57-66% of the disposal of m-DNB. Liver slices also produced 2(or 4)-amino-4(or 2)-nitrophenol, which was not detected in brain slices. We detected nitrosonitrobenzene in the slices from both parts of brain , but not in liver slices. The glucose consumption of brain slices fro m both areas were significantly increased in the presence of m-DNB: by 26% in the brain stem (p<0.001) and by 17.9% in cerebral cortex (p<0. 01). This may be considered a pre-cytotoxic effect. The results demons trate that brain has considerable nitroreductive capacity towards m-DN B, and that in situ reduction of m-DNB may be responsible for its neur otoxicity. (C) 1997 Inter Press, Inc.