Biochemical and Morphologic Characterization of Acrylamide Peripheral Neuropathy

Ellen J. Lehning, Anita Persaud, Karen R. Dyer, Bernard S. Jortner, Richard M. LoPachin

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Abstract

To determine1 whether reduced Na+/K+-ATPase activity might be involved in acrylamide (ACR)-induced peripheral axon swelling and degeneration, rubidium (Rb+) transport was measured as an index of enzyme function, x-ray microanalysis was used to quantify elemental Rb uptake and accumulation in internodal myelinated axons, mitochondria, Schwann cells, and myelin of rat tibial nerve cryosections. Results demonstrated impairment of Rb uptake in tibial axons from orally intoxicated (2.8 mM ACR for 34 days), moderately affected rats. In severely affected oral rats (49 days), complete inhibition of Rb transport and frank axon degeneration were evident. However, in moderate-to-severely affected rats exposed to ACR via ip injection (50 mg/kg/day for 11 days), neither structural nor enzymatic changes were present in tibial fibers. These findings in nerve cryosections suggested inhibition of axolemmal Na+ pump activity and degeneration were dependent upon route of ACR administration. This possibility was substantiated by a quantitative longitudinal morphometric study of conventionally fixed tibial nerve. Oral ACR treatment (2.8 mM ACR for 15-49 days) was associated with progressive axon degeneration, which was preceded by atrophy. Axonal swellings were rarely (< 1%) observed. In contrast, ip ACR injection (50 mg/kg/day for 5-11 days) produced classic behavioral neurotoxicity but did not alter axon morphology in tibial nerve. Thus, fiber degeneration and decreased Na+ pump activity were consequences of subchronic oral ACR administration. This parallel expression suggests a mechanistic relationship. However, the corresponding general neurotoxicological significance is unclear since, behavioral toxicity induced by ip ACR develops without structural and enzymatic changes in tibial nerve.

Original languageEnglish (US)
Pages (from-to)211-221
Number of pages11
JournalToxicology and Applied Pharmacology
Volume151
Issue number2
DOIs
Publication statusPublished - Aug 1998

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Keywords

  • Acrylamide
  • Axon degeneration
  • Axon swelling
  • Na/K-ATPase
  • Rubidium transport
  • Toxic distal axonopathy

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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