The etiology of acrylamide neuropathy: Enolase, phosphofructokinase, and glyceraldehyde-3-phosphate dehydrogenase activities in peripheral nerve, spinal cord, brain, and skeletal muscle of acrylamide-intoxicated cats

Abstract

Previous studies have shown that the neurotoxin, acrylamide, inhibits several glycolytic enzymes when tested in vitro and that the activity of neuron-specific enolase (NSE) is decreased in rats treated with neurotoxic doses of acrylamide. To determine whether the effect on NSE was species specific and whether glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphofructokinase (PFK) activities were decreased in vivo, cats were treated with either 15 or 30 mg/kg/day of acrylamide for 10 days. Twenty-four hours after the last injection, samples of sciatic nerve, brain, spinal cord, and skeletal muscle were assayed for total enolase, NSE, GAPDH, and PFK activities. The low and high doses of acrylamide resulted in the following respective decreases in NSE activity: 62.1 and 69.7% in the distal peripheral nerve and 37.1 and 45.4% in brain. GAPDH activity was similarly depressed in brain and both proximal and distal portions of the sciatic nerve. Additionally, all other tissues showed significant reductions in GAPDH. Neither total enolase activity of peripheral nerve, spinal cord, and skeletal muscle nor PFK activity in these tissues and in brain was decreased. In contrast, PFK in gastrocnemius muscle was increased 700% by the high dose of acrylamide, which may represent a compensatory mechanism. These data support the hypothesis that the mechanism of the toxic action of acrylamide involves inhibition of glycolysis at two enzymatic sites and that the selectivity exhibited by the toxic agent resides in its ability to inhibit a neuron-specific isoenzyme.