Acrylamide disrupts elemental composition and water content of rat tibial nerve. I. Myelinated axons.
The mechanism by which acrylamide (ACR) produces distal axonopathy in humans and laboratory animals is unknown. The possibility that this neuropathy involves deregulation of elements and water in rat peripheral nerve has been investigated. Electron probe X-ray microanalysis was used to measure percentages of water and concentrations (mmol element/kg dry or wet wt) of Na, P, S, Cl, K, Ca, and Mg in axoplasm and mitochondrial areas of tibial nerve axons. Results show that when rats were intoxicated with ACR by either the oral (2.8 mM in drinking water, up to 60 days) or the intraperitoneal (ip, 50 mg/kg/day x 5 or 10 days) route, a progressive loss of internodal axoplasmic K, Cl, and Na regulation was observed in subpopulations of myelinated fibers. Elemental deregulation was manifest as a shift in mean elemental content, widening of the corresponding concentration range, and a statistically significant increase in data variance. In internodal axonal regions, elemental composition of mitochondrial areas was not altered by ip ACR intoxication, whereas oral exposure was associated with delayed changes in Na, K, Cl, Ca, and Mg. In swollen axons, axoplasm and mitochondrial areas exhibited complete loss of element and water compartmentalization. This global decompartmentalization of swollen axons was quantitatively similar regardless of the route or length of ACR exposure. The results of this study suggest that a progressive loss of elemental regulation in axoplasm of myelinated tibial nerve fibers might be mechanistically related to ACR neurotoxicity.
LoPachin
R M
RM
Department of Anesthesiology, Medical School, SUNY, Stony Brook 11794-8480.
Castiglia
C M
CM
Saubermann
A J
AJ
D020106:Acrylamide; D000178:Acrylamides / Q000633:toxicity*; D000818:Animals; D001369:Axons / Q000737:chemistry / Q000187:drug effects; D001834:Body Water / Q000187:drug effects*; D004577:Electron Probe Microanalysis; D007091:Image Processing, Computer-Assisted; D008297:Male; D008855:Microscopy, Electron, Scanning; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013979:Tibial Nerve / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D014131:Trace Elements / Q000378:metabolism
D000178:Acrylamides; D014131:Trace Elements; D020106:Acrylamide