NEUROTOXICITY OF GLYCIDAMIDE, AN ACRYLAMIDE METABOLITE, FOLLOWING INTRAPERITONEAL INJECTIONS IN RATS

Acrylamide (2-propenamide) monomer produces central-peripheral distal axonopathy in humans and some animal species. Its neurotoxicity is cha racterized by abnormal sensation, decreased motor strength, and ataxia . Acrylamide forms adducts with glutathione, proteins, and DNA. Recent studies demonstrated that acrylamide is metabolized to its epoxide, g lycidamide (2,3-epoxy-1-propanamide). We studied the neurotoxicity pot ential of glycidamide in male Sprague-Dawley rats. Animals (groups of 6) were injected ip daily with either aqueous acrylamide or glycidamid e at an acrylamide-equivalent dose of 50 mg/kg (0.70 mmol/kg). Both tr eatments resulted initially in the rats circling, which was followed b y the onset of ataxia at 7-9 d and hindlimb paralysis at 12-14 d. Trea ted animals showed muscle wasting. At termination, acrylamide- and gly cidamide-treated rats weighed 105% and 86% of initial weight, respecti vely, compared to 145% for controls. Animals were anesthetized and per fused with 10% neutral phosphate-buffered formalin 12 or 14 d after be ginning of treatment. Both treatment groups exhibited similar neuropat hologic changes in the central and peripheral nervous systems. More se vere lesions were produced by glycidamide. A marked increase in the nu mber of affected Purkinje cells in the cerebellum, which exhibited cha nges ranging from pyknosis to cell death, were present. The brainstem exhibited axonal degeneration with chromatolytic necrosis in midbrain medial and lateral reticular nuclei. The spinal cord was characterized by spongy form changes with vacuoles of different sizes in various le vels. These results suggest that glycidamide is an active neurotoxic m etabolite of acrylamide.