Effects of the hydroxyl radical scavenger, dimethylthiourea, on peripheral nerve tissue perfusion, conduction velocity and nociception in experimental diabetes
Open accessAbstract
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) x 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.
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Formation of hydroxyl radicals also contributes to impairment of vascular reactivity and nerve function in diabetes.
“Because metal chelators and hydroxyl radical scavengers have also been demonstrated to be effective in preventing diabetes-induced vascular and neural dysfunction, it is likely that the formation of hydroxyl radicals also contributes to impairment of vascular reactivity and nerve function in diabetes (46–51, 145).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [51]
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- Authors
- Cameron, N. E., Tuck, Z., McCabe, L., & Cotter, M. A.
- Affiliations
- University of Aberdeen (GB)
- Venue
- Diabetologia
- Published
- 2001-09-01
- Volume
- 44
- Issue
- 9
- Pages
- 1161-1169
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2061803566
- Cited by
- 97
- References
- 27
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 1 · 2015: 6 · 2014: 3 · 2013: 7 · 2012: 5
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- dimethylthiourea, hydroxyl radical scavengers, diabetic neuropathy, oxidative stress, nerve conduction velocity, nociception, hyperalgesia, diabetic vascular disease, antioxidant therapy, streptozotocin-induced diabetes, superior cervical ganglion, sciatic nerve
- MeSH terms
- Animals, Diabetes Mellitus, Experimental, Male, Mechanoreceptors, Neural Conduction, Nociceptors, Peripheral Nerves, Sciatic Nerve, Thiourea, Free Radical Scavengers, Rats, Sprague-Dawley, Hydroxyl Radical, Superior Cervical Ganglion, Oxidative Stress, Rats
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