Biochemical and Morphologic Characterization of Acrylamide Peripheral Neuropathy

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

Research output: Contribution to journalArticle

65 Citations (Scopus)

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
StatePublished - Aug 1998

Fingerprint

Acrylamide
Peripheral Nervous System Diseases
Axons
Tibial Nerve
Rats
Swelling
Pumps
Rubidium
Injections
Mitochondria
Fibers
Schwann Cells
Myelin Sheath
Atrophy
Oral Administration
Longitudinal Studies
Toxicity
Adenosine Triphosphatases
Cells
X-Rays

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Biochemical and Morphologic Characterization of Acrylamide Peripheral Neuropathy. / Lehning, Ellen J.; Persaud, Anita; Dyer, Karen R.; Jortner, Bernard S.; LoPachin, Richard M.

In: Toxicology and Applied Pharmacology, Vol. 151, No. 2, 08.1998, p. 211-221.

Research output: Contribution to journalArticle

Lehning, EJ, Persaud, A, Dyer, KR, Jortner, BS & LoPachin, RM 1998, 'Biochemical and Morphologic Characterization of Acrylamide Peripheral Neuropathy', Toxicology and Applied Pharmacology, vol. 151, no. 2, pp. 211-221.
Lehning, Ellen J. ; Persaud, Anita ; Dyer, Karen R. ; Jortner, Bernard S. ; LoPachin, Richard M. / Biochemical and Morphologic Characterization of Acrylamide Peripheral Neuropathy. In: Toxicology and Applied Pharmacology. 1998 ; Vol. 151, No. 2. pp. 211-221.
@article{02afe58dc5c1433a9b197925720215e0,
title = "Biochemical and Morphologic Characterization of Acrylamide Peripheral Neuropathy",
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.",
keywords = "Acrylamide, Axon degeneration, Axon swelling, Na/K-ATPase, Rubidium transport, Toxic distal axonopathy",
author = "Lehning, {Ellen J.} and Anita Persaud and Dyer, {Karen R.} and Jortner, {Bernard S.} and LoPachin, {Richard M.}",
year = "1998",
month = "8",
language = "English (US)",
volume = "151",
pages = "211--221",
journal = "Toxicology and Applied Pharmacology",
issn = "0041-008X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Biochemical and Morphologic Characterization of Acrylamide Peripheral Neuropathy

AU - Lehning, Ellen J.

AU - Persaud, Anita

AU - Dyer, Karen R.

AU - Jortner, Bernard S.

AU - LoPachin, Richard M.

PY - 1998/8

Y1 - 1998/8

N2 - 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.

AB - 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.

KW - Acrylamide

KW - Axon degeneration

KW - Axon swelling

KW - Na/K-ATPase

KW - Rubidium transport

KW - Toxic distal axonopathy

UR - http://www.scopus.com/inward/record.url?scp=0032138195&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032138195&partnerID=8YFLogxK

M3 - Article

VL - 151

SP - 211

EP - 221

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 2

ER -