Administration of carnosine in the treatment of acute spinal cord injury(603 views) Di Paola R, Impellizzeri D, Salinaro AT, Mazzon E, Bellia F, Cavallaro M, Cornelius C, Vecchio G, Calabrese V, Rizzarelli E, Cuzzocrea S
Keywords: Apoptosis, Carnosine, Inflammation, Spinal Cord Injury, 3 Nitrotyrosine, Cytokine, Fas Ligand, Heat Shock Protein 70, Inducible Nitric Oxide Synthase, Myeloperoxidase, Protein Bax, Protein Bcl 2, Fas Antigen, Protein S100b, Aneurysm Clip, Animal Experiment, Animal Model, Animal Tissue, Conference Paper, Controlled Study, Drug Efficacy, Enzyme Activity, Immunoreactivity, Laminectomy, Mouse, Myelitis, Neutrophil Chemotaxis, Nick End Labeling, Nonhuman, Priority Journal, Protein Expression, Tissue Injury, Immunohistochemistry, Injury Severity, Spinal Cord Compression, Staining, Western Blotting, Bcl-2-Associated X Protein, Dose-Response Relationship, Fas Ligand Protein, Gene Expression Regulation, Proto-Oncogene Proteins C-Bcl-2, Spinal Cord Injuries,
Affiliations: *** IBB - CNR ***
IRCCS Centro Neurolesi Bonino-Pulejo, Via Palermo C.Da Casazza, 98100 Messina, Italy. dipaolar@unime.it
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, via C. Valeria (Gazzi), 98125 Messina, Italy
Department of Chemical Sciences, University of Catania, Viale Andrea Doria, 6, 95125 Catania, Italy
Interuniversity Consortium INBB, Catania, Italy
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Administration of carnosine in the treatment of acute spinal cord injury
L-Carnosine is an endogenously synthesized dipeptide composed of beta-alanine and L-histidine. It acts as a free radical scavenger and possesses antioxidant properties. L-Carnosine reduces proinflammatory and profibrotic cytokines such as transforming growth factor-beta (TGF-beta), interleukin (IL)-1, and tumor necrosis factor (TNF)-alpha in different experimental settings. In the present study, we investigated the efficacy of L and D-carnosine on the animal model of spinal cord injury (SCI). The spinal cord was exposed via a four-level T5-T8 laminectomy and SCI was produced by extradural compression of the spinal cord at level T6-T7 using an aneurysm clip with a closing force of 24 g. Treatment with D-carnosine (150 mg/kg administered i.p., 1 h and 6h, after SCI), but not L-carnosine significantly decreased (a) the degree of spinal cord inflammation and tissue injury (histological score), (b) neutrophil infiltration (myeloperoxidase activity), (c) nitrotyrosine formation, inducible NO synthase (iNOS) and Hsp70 expression, (d) proinflammatory cytokines, and (e) apoptosis (TUNEL staining, Fas ligand, Bax, and Bcl-2 expression). Furthermore, D-carnosine (150 mg/kg administered i.p., 1 h and 6 h, after SCI) significantly ameliorated the loss of limb function (evaluated by motor recovery score). Taken together, our results demonstrate the strong difference between L-carnosine and D-carnosine. The result strongly suggests that D-carnosine treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma. Copyright 2011 Elsevier Inc. All rights reserved.
Administration of carnosine in the treatment of acute spinal cord injury
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