Acrylamide produces a direct, dose-dependent and specific inhibition of oxidative metabolism in motoneurons.
The mechanism of action of acrylamide (ACR) in producing a central-peripheral distal axonopathy is unknown. We have tested the hypothesis that ACR inhibition of enzymes of oxidative metabolism is responsible for compromise of the energy supply, thereby producing the neuropathy. A single 50 mg/kg i.p. dose of ACR resulted in a 33.4% decrease in NADH-tetrazolium reductase (NADH-TR) (indicative of oxidative metabolism) activity in rat soleus motoneurons within one hour of injection. Methylene bis ACR (Mb-ACR), a non-neurotoxic analogue, produced a much smaller (6.7%) decrease in NADH-TR activity. Restoration of normal NADH-TR activity following that single injection occurred in 3 days. In vitro histochemical assays demonstrated a dose-dependent inhibition of motoneuron NADH-TR activity (10-54%) by 1-10mM ACR. Equimolar Mb-ACR produced significantly less inhibition. The rapid, dose-dependent and specific inhibition of this oxidative enzyme activity by ACR provides evidence in support of the energy hypothesis of ACR-induced neuropathy and more specifically suggests that oxidative enzyme inhibitions are a critical site of ACR action.
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D020106:Acrylamide; D000178:Acrylamides / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009046:Motor Neurons / Q000187:drug effects* / Q000201:enzymology; D009246:NADH Tetrazolium Reductase / Q000037:antagonists & inhibitors*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D009422:Nervous System Diseases / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects
D000178:Acrylamides; D020106:Acrylamide; D009246:NADH Tetrazolium Reductase; D009247:NADH, NADPH Oxidoreductases; C021221:N,N'-methylenebisacrylamide