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Protective effect of orally administered carnosine on bleomycin-induced lung injury

¹Department of Internal Medicine and Specialistic Medicine, Section of Respiratory Diseases, University of Catania, Catania, Italy; ²Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy; ³Istituto di Ricovero e Cura a Carattere Scientifico Centro Neurolesi "Bonino-Pulejo," Messina, Italy; ⁴Department of Chemical Sciences, University of Catania, Italy, Catania, Italy; ⁵Institute of Biostructures and Bioimages, Consiglio Nazionale delle Ricerche, Catania, Italy

Submitted 27 July 2006 ; accepted in final form 3 January 2007

Carnosine is an endogenously synthesized dipeptide composed of -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- (TGF-), IL-1, and TNF- 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- levels, lung histology, and immunohistochemical analyses for myeloperoxidase, TGF-, 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-, inducible nitric oxide synthase, nitrotyrosine, and poly(ADP-ribose) polymerase immunostaining, 7) BAL TGF- 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.

lung fibrosis; oxidative stress; chelating agent

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