The influence of systemic factors on acrylamide-induced changes in brain, nerve, and other tissues.

In order to define the locus of acrylamide neurotoxicity, the effects of chronic intoxication (total dose 500 mg/kg) on cholinergic synthesis and transport, the Schwann cell-myelin complex, lysosomal activity, and several metabolic pathways were determined in rat sciatic nerve, spinal cord, and brain. No changes were found in hematological measures or in the levels of clinically important blood enzymes, indicating no major damage to other organs. The activities of choline acetyltransferase (ChAT), 2',3'-cyclic nucleotide phosphohydrolase, beta-glucuronidase, and lactate dehydrogenase were unaffected in acrylamide paralyzed animals, but creatine kinase (CK) decreased in sciatic nerve, muscle, and brain, particularly in animals dying of the intoxication. CK blood and the CK isoenzyme patterns in blood were unchanged. The synthesis of protein in brain and spinal cord (measured in vivo) were decreased in rats exposed to high-dose acrylamide. However, in brain and cord, CK decreased only after animals became systemically ill and suffered weight loss, with the lowest activities in those animals sick enough to die. The degree of stress to which the animals had been subjected was indicated by enlargement of the adrenal glands and decreased sulfolipid synthesis in the adrenals. Rats exposed to 25 mg/kg/day acrylamide to a total dose of 250 mg/kg developed leg weakness but not paralysis or weight loss and had a 25% decrease in CK only in the distal sciatic nerve. Because of the apparently stress-related or agonal loss of CK, no specific effect of acrylamide on the enzyme could be definitely demonstrated. Neither could the changes in protein synthesis be attributed solely to a direct effect of the toxin. These results illustrate the difficulties encountered in interpreting intoxication studies that produce systemic illness and support the suggestion that CK activity may be a useful marker of the severity and duration of the agonal state in studies of postmortem human brain.