The Pathokinetics of Acrylamide Intoxication: A Reassessment of the Problem

Abstract

Acrylamide was given intraperitoneally to rats (30 mg/kg/day, five times/week) for 3 weeks, and the nervous and muscle tissues were examined by conventional methods over 5 weeks. Three striking cellular changes were observed. 1 Scattered degeneration of many Purkinje cells from 5 days onwards. 2 Widespread swelling and argyrophilia of nerve terminals from 10 days in both PNS and CNS. Motor and sensory endings were equally affected in all muscles examined. Synaptic and preterminal swelling also occurred in spinal cord, brain stem, and in certain cerebellar terminals. Degeneration occasionally followed this change, particularly in sensory nerve fibres, but not necessarily. 3 Chromatolysis in spinal ganglion cells and occasionally in anterior horn cells from 7 days onwards before the onset of axonal degeneration. This unique sequence of events is discussed in the light of the metabolic and other changes described by earlier authors.

Hazardous effects of fried potato chips on the development of retina in albino rats

“…Intoxication at a lower dose rate was associated with initial nerve terminal degeneration followed later by pre-terminal axon degeneration. These findings are consistent with other evidences suggesting that, regardless of dose-rate, nerve terminal degeneration was an initial consequence of ACR intoxication in both CNS [26] and PNS [27] . Experimental ACRintoxication in mice [28] and rat [29] was found to produce a pronounced neuropathy characterized by flaccid paralysis and ataxia.…”

Scientific Opinion on acrylamide in food

“…The neurotoxic action of AA was suggested to be due to effects on cells of the central and peripheral nervous system including changes in cellular metabolism (Howland et al, 1980;Brimijoin and Hammond,1985;Medrano and LoPachin, 1989;Exon, 2006), changes in gene transcription and protein synthesis (Cavanagh and Nolan, 1982a,b;Cavanagh, 1982;Cavanagh and Gysbers, 1983;Bisby and Redshaw, 1987;Lin et al, 2000;El-Alfy et al, 2011;Seale et al, 2012), effects on neurotransmitter levels and turn-over (Dixit et al, 1981;Uphouse and Russell, 1981;Aldous et al, 1983;Shi et al, 2012), binding to cellular proteins including damage to microtubular and neurofilamental proteins (Hashimoto and Aldridge, 1970;Tanii and Hashimoto, 1983;Carrington et al, 1991;Reagan et al, 1994;Abou-Donia, 1996, 1997;Lapadula et al, 1989;Xiwen et al, 1992), changes in ion distribution (Lehning et al, 1998;LoPachin and Lehning, 1994), and axonal transport (Chretien et al, 1981;Miller and Spencer, 1984;Gold et al, 1985;Moretto and Sabri, 1988;Logan and McLean, 1988;Harry et al, 1989;Sabri and Spencer, 1990;Martenson et al, 1995;Sickles et al, 1995Sickles et al, ,1996Stone et al, 2001). However, the minimal effects of AA-treatment, by up to a maximally tolerated dose, on: (i) gene expression related to cholinergic, noradrenergic, dopaminergic, GABAergic, or glutamatergic neurotransmitter systems; (ii) neurotransmitter levels related ...…”

Neuropathological Evaluation of Acrylamide- and 3,3'-Iminodipropionitrile-Induced Neurotoxicity in a Rat 28-Day Oral Toxicity Study-Collaborative Project for Standardization of Test Procedures and Evaluation of Neurotoxicity.

“…Acrylamide-induced neurotoxicity is characterized as "distal axonopathy" targeting medium-and large-sized myelinated nerve fibers, and lesions of nerve fibers are noted as Wallerian-like nerve degeneration with axonal atrophy and/or swelling and disintegration of myelin sheaths 8,9 . In addition, acrylamide induces chromatolysis in ganglion neurons, and Purkinje's cell necrosis in the cerebellum [10][11][12] . These lesions in the peripheral and central nervous system are associated with functional abnormalities such as sensory loss and muscular weakness 13 .…”