Capacity of rat brain to metabolize m-dinitrobenzene: an in vitro study.
m-dinitrobenzene (m-DNB) is a neurotoxin producing selective brain lesions, 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-DNB and its metabolites were detected by HPLC, and identified by either HPLC or Mass Spectrometry (MS). All three types of tissues showed metabolic activity towards m-DNB. Metabolic disposal of m-DNB was 1.05 +/- 0.11 mumol/g wet weight/h in liver, 0.49 +/- 0.05 in brain stem, and 0.44 +/- 0.05 in forebrain (mean +/- SD, n = 4). m-Nitroaniline was found to be the main metabolite produced by both brain and liver slices, representing 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 from 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 demonstrate that brain has considerable nitroreductive capacity towards m-DNB, and that in situ reduction of m-DNB may be responsible for its neurotoxicity.
Hu
H L
HL
Medical Research Council Toxicology Unit, Leicester, UK.
Bennett
N
N
Lamb
J H
JH
Ghersi-Egea
J F
JF
Schlosshauer
B
B
Ray
D E
DE
D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004136:Dinitrobenzenes / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013056:Spectrophotometry, Ultraviolet
D004136:Dinitrobenzenes; C017906:3-dinitrobenzene; D005947:Glucose