Protective effect of orally administered carnosine on bleomycin-induced lung injury
| Autor: | Salvatore Cuzzocrea, 2, 3* Tiziana Genovese, 3* Marco Failla, 1 Graziella Vecchio, 4 Mary Fruciano, 1 Emanuela Mazzon, 3 Rosanna Di Paola, 3 Carmelo Muia`, 3 Cristina La Rosa, 1 Nunzio Crimi, 1 Enrico Rizzarelli, 4, 5, Carlo Vancheri1 |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Antioxidant Physiology Biopsy Pulmonary Fibrosis medicine.medical_treatment Administration Oral Carnosine Lung injury Pharmacology medicine.disease_cause Bleomycin Proinflammatory cytokine Mice chemistry.chemical_compound Physiology (medical) medicine Animals oxidative stress Lung Inflammation Dipeptide business.industry lung fibrosis Lung Injury Cell Biology respiratory system Free radical scavenger respiratory tract diseases chelating agent chemistry Models Animal Immunology business Oxidative stress |
| Zdroj: | American journal of physiology. Lung cellular and molecular physiology 292 (2007): L1095–L1104. doi:10.1152/ajplung.00283.2006 info:cnr-pdr/source/autori:Salvatore Cuzzocrea,2,3* Tiziana Genovese,2,3* Marco Failla,1 Graziella Vecchio,4 Mary Fruciano,1 Emanuela Mazzon,2,3 Rosanna Di Paola,2,3 Carmelo Muia`,2,3 Cristina La Rosa,1 Nunzio Crimi,1 Enrico Rizzarelli,4,5 and Carlo Vancheri1/titolo:Protective effect of orally administered carnosine on bleomycin-induced lung injury/doi:10.1152%2Fajplung.00283.2006/rivista:American journal of physiology. Lung cellular and molecular physiology/anno:2007/pagina_da:L1095/pagina_a:L1104/intervallo_pagine:L1095–L1104/volume:292 |
| Popis: | Carnosine is an endogenously synthesized dipeptide composed of beta-alanine and L-histidine. It acts as a free radical scavenger and possesses antioxidant properties. Carnosine reduces proinflammatory and profibrotic cytokines such as transforming growth factor-beta (TGF-beta), IL-1, and TNF-alpha in different experimental settings. In the present study, we investigated the efficacy of carnosine on the animal model of bleomycin-induced lung injury. Mice were subjected to intratracheal administration of bleomycin and were assigned to receive carnosine daily by an oral bolus of 150 mg/kg. One week after fibrosis induction, bronchoalveolar lavage (BAL) cell counts and TGF-beta levels, lung histology, and immunohistochemical analyses for myeloperoxidase, TGF-beta, inducible nitric oxide synthase, nitrotyrosine, and poly(ADP-ribose) polymerase were performed. Finally, apoptosis was quantified by terminal deoxynucleotidyltransferase-mediated UTP end-labeling assay. After bleomycin administration, carnosine- treated mice exhibited a reduced degree of lung damage and inflammation compared with wild-type mice, as shown by the reduction of 1) body weight, 2) mortality rate, 3) lung infiltration by neutrophils ( myeloperoxidase activity and BAL total and differential cell counts), 4) lung edema, 5) histological evidence of lung injury and collagen deposition, 6) lung myeloperoxidase, TGF-beta, inducible nitric oxide synthase, nitrotyrosine, and poly(ADP-ribose) polymerase immunostaining, 7) BAL TGF-beta levels, and 8) apoptosis. Our results indicate that orally administered carnosine is able to prevent bleomycin-induced lung injury likely through its direct antioxidant properties. Carnosine is already available for human use. It might prove useful as an add-on therapy for the treatment of fibrotic disorders of the lung where oxidative stress plays a role, such as for idiopathic pulmonary fibrosis, a disease that still represents a major challenge to medical treatment. |
| Databáze: | OpenAIRE |
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