Abstract
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 6 h, 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1478-1489 |
| Number of pages | 12 |
| Journal | Biochemical Pharmacology |
| Volume | 82 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Nov 15 2011 |
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Keywords
- Apoptosis
- Carnosine
- Inflammation
- Spinal cord injury
ASJC Scopus subject areas
- Pharmacology
- Biochemistry
Cite this
Administration of carnosine in the treatment of acute spinal cord injury. / Di Paola, Rosanna; Impellizzeri, Daniela; Salinaro, Angela Trovato; Mazzon, Emanuela; Bellia, Francesco; Cavallaro, Monia; Cornelius, Carolin; Vecchio, Graziella; Calabrese, Vittorio; Rizzarelli, Enrico; Cuzzocrea, Salvatore.
In: Biochemical Pharmacology, Vol. 82, No. 10, 15.11.2011, p. 1478-1489.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Administration of carnosine in the treatment of acute spinal cord injury
AU - Di Paola, Rosanna
AU - Impellizzeri, Daniela
AU - Salinaro, Angela Trovato
AU - Mazzon, Emanuela
AU - Bellia, Francesco
AU - Cavallaro, Monia
AU - Cornelius, Carolin
AU - Vecchio, Graziella
AU - Calabrese, Vittorio
AU - Rizzarelli, Enrico
AU - Cuzzocrea, Salvatore
PY - 2011/11/15
Y1 - 2011/11/15
N2 - 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 6 h, 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.
AB - 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 6 h, 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.
KW - Apoptosis
KW - Carnosine
KW - Inflammation
KW - Spinal cord injury
UR - http://www.scopus.com/inward/record.url?scp=80054715568&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80054715568&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2011.07.074
DO - 10.1016/j.bcp.2011.07.074
M3 - Article
C2 - 21787762
AN - SCOPUS:80054715568
VL - 82
SP - 1478
EP - 1489
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 10
ER -