1,3-Dinitrobenzene-induced encephalopathy in rats

Exposure to 1,3-dinitrobenzene (1,3-DNB) in humans induces methaemoglobinaemia, nausea and nervous symptoms. When given to conventional rats, twice-daily oral doses of 10 mg kg-1 1,3-DNB produce methaemoglobinaemia and frequently ataxia after four or five doses. In germ free rats given only a single oral dose of 20 mg kg-1, similar symptoms occur but are of more rapid onset. Light and electron microscope examinations reveal an acute thiamine deficiency-like lesion in the brain stems of both ataxic and apparently normal rats. Bilaterally symmetrical vacuolated lesions involve cerebellar roof, vestibular and superior olivary nuclei and the inferior colliculi. Frequent petechial haemorrhages are associated with these lesions, the erythrocytes usually being limited to enlarged Virchow-Robin spaces but sometimes spreading more widely. The primary cellular targets appear to be astrocytes, oligodendrocytes and vascular elements with secondary neuronal involvement. It is suggested that 1,3-DNB interferes with intracellular redox mechanisms resulting in impaired glucose oxidation.