Effects of the hydroxyl radical scavenger, dimethylthiourea, on peripheral nerve tissue perfusion, conduction velocity and nociception in experimental diabetes

Norman E Cameron, Z. Tuck, L. McCabe, Mary Anne Cotter

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Aims/hypothesis. Increased oxidative stress has been linked to diabetic neurovascular complications, which are reduced by antioxidants. Our aim was to assess the contribution of hydroxyl radicals to early neuropathic changes by examining the effects of treatment with the specific scavenger, dimethylthiourea, on nerve function and neural tissue blood flow in diabetic rats. Methods. Diabetes was induced by streptozotocin. Measurements comprised sciatic nerve motor and saphenous nerve sensory conduction velocity. Responses to noxious mechanical and thermal stimuli were estimated by Randall-Sellito and Hargreaves tests respectively. Sciatic nerve and superior cervical ganglion blood flow were measured by hydrogen clearance microelectrode polarography. Results. Eight weeks of diabetes reduced motor and sensory conduction velocity by 19.9 % and 15.7 % respectively, and these were completely corrected by 2 weeks of dimethylthiourea treatment. The ED50 for motor conduction was 9 mg (.) kg(-1) (.) day(-1). Mechanical and thermal nociceptive sensitivities were 18.9 % and 25.0 % increased by diabetes, respectively, indicating hyperalgesia which was 70 % reduced by dimethylthiourea. Sciatic endoneurial and superior cervical ganglion blood flows were 51.2 % and 52.4 % reduced by diabetes and there was an approximately 80 % improvement with treatment. Conclusion/interpretation. Hydroxyl radicals seem to make a major contribution to neuropathy and vasculopathy in diabetic rats. Treatment with the hydroxyl scavenger, dimethylthiourea, was highly effective. The data suggest that the development of potent hydroxyl radical scavengers suitable for use in man could markedly enhance the potential therapeutic value of an antioxidant approach to the treatment of diabetic neuropathy and vascular disease.

Original languageEnglish
Pages (from-to)1161-1169
Number of pages8
JournalDiabetologia
Volume44
Issue number9
DOIs
Publication statusPublished - Sep 2001

Keywords

  • neuropathy
  • pain
  • nerve conduction
  • blood flow
  • autonomic ganglion
  • oxidative stress
  • hydroxyl radical
  • dimethylthiourea
  • diabetic rat
  • ALPHA-LIPOIC ACID
  • ALDOSE REDUCTASE INHIBITION
  • ENDOTHELIUM-DEPENDENT RELAXATION
  • NITRIC-OXIDE
  • BLOOD-FLOW
  • NEUROVASCULAR FUNCTION
  • POTENTIAL CONTRIBUTION
  • AUTONOMIC NEUROPATHY
  • CORPUS CAVERNOSUM
  • HYDROGEN-PEROXIDE

Cite this

Effects of the hydroxyl radical scavenger, dimethylthiourea, on peripheral nerve tissue perfusion, conduction velocity and nociception in experimental diabetes. / Cameron, Norman E; Tuck, Z.; McCabe, L.; Cotter, Mary Anne.

In: Diabetologia, Vol. 44, No. 9, 09.2001, p. 1161-1169.

Research output: Contribution to journalArticle

@article{ddbb0582b170480981a919f8fddbcf7b,
title = "Effects of the hydroxyl radical scavenger, dimethylthiourea, on peripheral nerve tissue perfusion, conduction velocity and nociception in experimental diabetes",
abstract = "Aims/hypothesis. Increased oxidative stress has been linked to diabetic neurovascular complications, which are reduced by antioxidants. Our aim was to assess the contribution of hydroxyl radicals to early neuropathic changes by examining the effects of treatment with the specific scavenger, dimethylthiourea, on nerve function and neural tissue blood flow in diabetic rats. Methods. Diabetes was induced by streptozotocin. Measurements comprised sciatic nerve motor and saphenous nerve sensory conduction velocity. Responses to noxious mechanical and thermal stimuli were estimated by Randall-Sellito and Hargreaves tests respectively. Sciatic nerve and superior cervical ganglion blood flow were measured by hydrogen clearance microelectrode polarography. Results. Eight weeks of diabetes reduced motor and sensory conduction velocity by 19.9 {\%} and 15.7 {\%} respectively, and these were completely corrected by 2 weeks of dimethylthiourea treatment. The ED50 for motor conduction was 9 mg (.) kg(-1) (.) day(-1). Mechanical and thermal nociceptive sensitivities were 18.9 {\%} and 25.0 {\%} increased by diabetes, respectively, indicating hyperalgesia which was 70 {\%} reduced by dimethylthiourea. Sciatic endoneurial and superior cervical ganglion blood flows were 51.2 {\%} and 52.4 {\%} reduced by diabetes and there was an approximately 80 {\%} improvement with treatment. Conclusion/interpretation. Hydroxyl radicals seem to make a major contribution to neuropathy and vasculopathy in diabetic rats. Treatment with the hydroxyl scavenger, dimethylthiourea, was highly effective. The data suggest that the development of potent hydroxyl radical scavengers suitable for use in man could markedly enhance the potential therapeutic value of an antioxidant approach to the treatment of diabetic neuropathy and vascular disease.",
keywords = "neuropathy, pain, nerve conduction, blood flow, autonomic ganglion, oxidative stress, hydroxyl radical, dimethylthiourea, diabetic rat, ALPHA-LIPOIC ACID, ALDOSE REDUCTASE INHIBITION, ENDOTHELIUM-DEPENDENT RELAXATION, NITRIC-OXIDE, BLOOD-FLOW, NEUROVASCULAR FUNCTION, POTENTIAL CONTRIBUTION, AUTONOMIC NEUROPATHY, CORPUS CAVERNOSUM, HYDROGEN-PEROXIDE",
author = "Cameron, {Norman E} and Z. Tuck and L. McCabe and Cotter, {Mary Anne}",
year = "2001",
month = "9",
doi = "10.1007/s001250100626",
language = "English",
volume = "44",
pages = "1161--1169",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer",
number = "9",

}

TY - JOUR

T1 - Effects of the hydroxyl radical scavenger, dimethylthiourea, on peripheral nerve tissue perfusion, conduction velocity and nociception in experimental diabetes

AU - Cameron, Norman E

AU - Tuck, Z.

AU - McCabe, L.

AU - Cotter, Mary Anne

PY - 2001/9

Y1 - 2001/9

N2 - Aims/hypothesis. Increased oxidative stress has been linked to diabetic neurovascular complications, which are reduced by antioxidants. Our aim was to assess the contribution of hydroxyl radicals to early neuropathic changes by examining the effects of treatment with the specific scavenger, dimethylthiourea, on nerve function and neural tissue blood flow in diabetic rats. Methods. Diabetes was induced by streptozotocin. Measurements comprised sciatic nerve motor and saphenous nerve sensory conduction velocity. Responses to noxious mechanical and thermal stimuli were estimated by Randall-Sellito and Hargreaves tests respectively. Sciatic nerve and superior cervical ganglion blood flow were measured by hydrogen clearance microelectrode polarography. Results. Eight weeks of diabetes reduced motor and sensory conduction velocity by 19.9 % and 15.7 % respectively, and these were completely corrected by 2 weeks of dimethylthiourea treatment. The ED50 for motor conduction was 9 mg (.) kg(-1) (.) day(-1). Mechanical and thermal nociceptive sensitivities were 18.9 % and 25.0 % increased by diabetes, respectively, indicating hyperalgesia which was 70 % reduced by dimethylthiourea. Sciatic endoneurial and superior cervical ganglion blood flows were 51.2 % and 52.4 % reduced by diabetes and there was an approximately 80 % improvement with treatment. Conclusion/interpretation. Hydroxyl radicals seem to make a major contribution to neuropathy and vasculopathy in diabetic rats. Treatment with the hydroxyl scavenger, dimethylthiourea, was highly effective. The data suggest that the development of potent hydroxyl radical scavengers suitable for use in man could markedly enhance the potential therapeutic value of an antioxidant approach to the treatment of diabetic neuropathy and vascular disease.

AB - Aims/hypothesis. Increased oxidative stress has been linked to diabetic neurovascular complications, which are reduced by antioxidants. Our aim was to assess the contribution of hydroxyl radicals to early neuropathic changes by examining the effects of treatment with the specific scavenger, dimethylthiourea, on nerve function and neural tissue blood flow in diabetic rats. Methods. Diabetes was induced by streptozotocin. Measurements comprised sciatic nerve motor and saphenous nerve sensory conduction velocity. Responses to noxious mechanical and thermal stimuli were estimated by Randall-Sellito and Hargreaves tests respectively. Sciatic nerve and superior cervical ganglion blood flow were measured by hydrogen clearance microelectrode polarography. Results. Eight weeks of diabetes reduced motor and sensory conduction velocity by 19.9 % and 15.7 % respectively, and these were completely corrected by 2 weeks of dimethylthiourea treatment. The ED50 for motor conduction was 9 mg (.) kg(-1) (.) day(-1). Mechanical and thermal nociceptive sensitivities were 18.9 % and 25.0 % increased by diabetes, respectively, indicating hyperalgesia which was 70 % reduced by dimethylthiourea. Sciatic endoneurial and superior cervical ganglion blood flows were 51.2 % and 52.4 % reduced by diabetes and there was an approximately 80 % improvement with treatment. Conclusion/interpretation. Hydroxyl radicals seem to make a major contribution to neuropathy and vasculopathy in diabetic rats. Treatment with the hydroxyl scavenger, dimethylthiourea, was highly effective. The data suggest that the development of potent hydroxyl radical scavengers suitable for use in man could markedly enhance the potential therapeutic value of an antioxidant approach to the treatment of diabetic neuropathy and vascular disease.

KW - neuropathy

KW - pain

KW - nerve conduction

KW - blood flow

KW - autonomic ganglion

KW - oxidative stress

KW - hydroxyl radical

KW - dimethylthiourea

KW - diabetic rat

KW - ALPHA-LIPOIC ACID

KW - ALDOSE REDUCTASE INHIBITION

KW - ENDOTHELIUM-DEPENDENT RELAXATION

KW - NITRIC-OXIDE

KW - BLOOD-FLOW

KW - NEUROVASCULAR FUNCTION

KW - POTENTIAL CONTRIBUTION

KW - AUTONOMIC NEUROPATHY

KW - CORPUS CAVERNOSUM

KW - HYDROGEN-PEROXIDE

U2 - 10.1007/s001250100626

DO - 10.1007/s001250100626

M3 - Article

VL - 44

SP - 1161

EP - 1169

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 9

ER -