Document Detail

Role for nitrosative stress in diabetic neuropathy: evidence from studies with a peroxynitrite decomposition catalyst.
MedLine Citation:
PMID:  15611153     Owner:  NLM     Status:  MEDLINE    
Nitrosative stress, that is, enhanced peroxynitrite formation, has been documented in both experimental and clinical diabetic neuropathy (DN), but its pathogenetic role remains unexplored. This study evaluated the role for nitrosative stress in two animal models of type 1 diabetes: streptozotocin-diabetic mice and diabetic NOD mice. Control (C) and streptozotocin-diabetic (D) mice were treated with and without the potent peroxynitrite decomposition catalyst FP15 (5 mg kg(-1) d(-1)) for 1 wk after 8 wk without treatment. Sciatic nerve nitrotyrosine (a marker of peroxynitrite-induced injury) and poly(ADP-ribose) immunoreactivities were present in D and absent in C and D+FP15. FP15 treatment corrected sciatic motor and hind-limb digital sensory nerve conduction deficits and sciatic nerve energy state in D, without affecting those variables in C. Nerve glucose and sorbitol pathway intermediate concentrations were similarly elevated in D and D+FP15 vs C. In diabetic NOD mice, a 7-day treatment with either 1 or 3 mg kg(-1) d(-1) FP15 reversed increased tail-flick latency (a sign of reduced pain sensitivity); the effect of the higher dose was significant as early as 3 days after beginning of the treatment. In conclusion, nitrosative stress plays a major role in DN in, at least, type 1 diabetes. This provides the rationale for development of agents counteracting peroxynitrite formation and promoting peroxynitrite decomposition, and their evaluation in DN.
Irina G Obrosova; Jon G Mabley; Zsuzsanna Zsengellér; Tamara Charniauskaya; Omorodola I Abatan; John T Groves; Csaba Szabó
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-12-20
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  19     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-04     Completed Date:  2005-10-25     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  401-3     Citation Subset:  IM    
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
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MeSH Terms
Blood Glucose / analysis
Creatine / analysis
Diabetes Mellitus, Experimental
Diabetes Mellitus, Type 1 / complications,  metabolism
Diabetic Neuropathies / etiology,  physiopathology*
Metalloporphyrins / pharmacology*
Mice, Inbred NOD
Neural Conduction / drug effects
Neurons, Afferent / physiology
Oxidative Stress / physiology*
Peroxynitrous Acid / metabolism*
Phosphocreatine / analysis
Poly(ADP-ribose) Polymerases / analysis
Reactive Nitrogen Species / physiology*
Sciatic Nerve / chemistry,  physiopathology
Tyrosine / analogs & derivatives,  analysis
Weight Gain / drug effects
Grant Support
Reg. No./Substance:
0/Blood Glucose; 0/FeCl tetrakis-2-(triethyleneglycolmonomethylether)pyridylporphyrin; 0/Metalloporphyrins; 0/Reactive Nitrogen Species; 14691-52-2/Peroxynitrous Acid; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; 57-00-1/Creatine; 67-07-2/Phosphocreatine; EC Polymerases; EC, mouse

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