EARLY METABOLIC CHANGES DURING M-DINITROBENZENE NEUROTOXICITY AND THEPOSSIBLE ROLE OF OXIDATIVE STRESS

m-Dinitrobenzene (m-DNB) is an industrial chemical causing gliovascula r lesions in the brain stem similar to those produced by nitroimidazol es and by thiamine deficiency. To identify early preneuropathic indice s of toxicity we examined the action of m-DNB On glycolysis and on mea sures of oxidative stress in the brain both in vivo and in vitro. Sign ificant increases in local cerebral glucose utilization were seen in 1 4 of 30 brain regions prior to development of lesions. Rat brain astro cyte cultures also showed increases in both glucose consumption and la ctic acid formation in the first 24 h following exposure to 0.5 mM m-D NB and prior to the development of cytotoxicity. The concentration of reduced glutathione in these cultures was decreased to about half of c ontrol values over a 2-h incubation period, indicating an early distur bance of redox balance. The rate of reduction of nitroblue tetrazolium increased eightfold during a 1-h incubation period, suggesting a free radical-mediated process. Superoxide dismutase partially prevented th is increase, although other protective agents failed to do so possibly due to lack of cellular penetration. These observations show that m-D NB neurotoxicity involves early metabolic stimulation and redox disrup tion that may be causally associated with the production of free radic als.