Subacute neurotoxicity of 5-fluorouracil and its derivative, carmofur, in cats

The subacute neurotoxicity of 5-fluorouracil (FU) and its derivative, carmofur (HCFU), in cats was morphologically examined; both these drugs were orally administered once daily for a maximum of three months. The dosis of FU and HCFU was 2 mg/kg/day and 10 mg/kg/day, respectively. Both FU and HCFU induced two sorts of changes in the brain, i.e., vacuolation and softening-like change. The former was distributed in the white matter of the cerebrum and cerebellum and in areas of the gray matter such as the tectum and tegmentum of the brain stem, while the latter was distributed exclusively in the gray matter of the tectum and tegmentum of the brain stem. The tectum, especially the inferior colliculus, was most frequently affected by both types of change. Ultrastructurally, vacuolation was found to be due to lamellar splitting or separation between the axon and innermost myelin layer. These findings were compared with those in dogs and as the etiopathogenesis vacuolation due to direct toxic effect of FU or its metabolites to myelin and softening-like change due to local circulatory disturbance caused by vacuolation were proposed.