| Melatonin modulates neuroinflammation and oxidative stress in experimental diabetic neuropathy: effects on NF-κB and Nrf2 cascades. | |
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MedLine Citation:
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PMID: 21062351 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Melatonin exhibits an array of biological activities, including antioxidant and anti-inflammatory actions. Diabetic neuropathy is one of the complications of diabetes with a prevalence rate of 50-60%. We have previously reported the protective effect of melatonin in experimental diabetic neuropathy. In this study, we investigated the role of nuclear factor-kappa B (NF-κB) and nuclear erythroid 2-related factor 2 (Nrf2) in melatonin-mediated protection against streptozotocin-induced diabetic neuropathy. Melatonin at doses of 3 and 10 mg/kg was administered daily in seventh and eighth week after diabetes induction. Motor nerve conduction velocity and nerve blood flow were improved in melatonin-treated animals. Melatonin also reduced the elevated expression of NF-κB, IκB-α, and phosphorylated IκB-α. Further, melatonin treatment also reduced the elevated levels of proinflammatory cytokines (TNF-α and IL-6), iNOS and COX-2 in sciatic nerves of animals. The capacity of melatonin to modulate Nrf2 pathway was associated with increased heme oxygenase-1 (HO-1) expression, which strengthens antioxidant defense. This fact was also established by decreased DNA fragmentation (because inhibition of excessive oxidant-induced DNA damage) in the sciatic nerve of melatonin-treated animals. The results of this study suggest that melatonin modulates neuroinflammation by decreasing NF-κB activation cascade and oxidative stress by increasing Nrf2 expression, which might be responsible at least in part, for its neuroprotective effect in diabetic neuropathy. |
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Authors:
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Geeta Negi; Ashutosh Kumar; Shyam S Sharma |
Publication Detail:
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Type: Journal Article Date: 2010-11-09 |
Journal Detail:
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Title: Journal of pineal research Volume: 50 ISSN: 1600-079X ISO Abbreviation: J. Pineal Res. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8504412 Medline TA: J Pineal Res Country: Denmark |
Other Details:
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Languages: eng Pagination: 124-31 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors. Journal of Pineal Research © 2010 John Wiley & Sons A/S. |
Affiliation:
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Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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