© 1987 Oxford University Press
research-article |
Monochloroacetic Acid Toxicity in the Mouse Associated with Blood-Brain Barrier Damage1,2
Joint Graduate Program in Toxicology, Rutgers University and UMDNJ/Rutgers Medical School Piscataway, New Jersey 08854 *Hercules Incorporated Wilmington Delaware 19894
Monochloroacetic acid (MCA) causes front paw rigidity in 10% of mice surviving a single oral toxic dose (320-380 mg/kg). Mice exhibiting front paw rigidity were killed at various times after MCA treatment and their brains were prepared for histological examination. As early as 48 hr post-treatment, RBCs were found outside capillaries in several brain regions, especially the cerebellum. At time points up to 8 weeks after MCA, extracapillary RBCs were seen to be undergoing lysis, and there was loss of cerebellar Purkinje cells. Three hours after oral administration of an LD8O of MCA (380mg/kg), entry of iv-injected [14C]inulin or [3 (1.0 µCi) into all brain regions was significantly increased compared to controls. Increased entry of into [14C]inulin the brains of mice occurred as early as 2 hr after MCA, coinciding with the onset of signs of toxicity, and remained elevated for up to 8 hr following treatment. Further studies revealed that only those mice which were moribund but not those which were unaffected by MCA (380 mg/kg) 4–6 hr after treatment had significantly increased brain levels of [14C]inulin or [3H]dopamine However, mice which survived an LD8O of MCA and exhibited front paw rigidity 24 hr later also had brain radiotracer concentrations significantly greater than controls. Both the lethal effects of MCA and the physical deficits observed in survivors may be associated with impairment of blood-brain barrier function.