title: Protective effects of S-nitrosoalbumin on lung injury induced by hypoxia-reoxygenation in mouse model of sickle cell disease.
abstract: Nitric oxide (NO) is a potential new therapeutic agent for sickle cell disease (SCD). We investigated the effects of NO donor on hypoxia-induced acute lung injury that occurs when transgenic sickle cell SAD mice are exposed to chronic hypoxia, a model for lung vasoocclusive sickle cell events. In wild-type and SAD mice, intraperitoneal injection of S-nitrosoalbumin (NO-Alb) produced no significant hematologic changes under room air conditions, whereas it induced mild temporary hypotension and inhibition of platelet aggregation. NO-Alb administration (300 mg/kg ip twice a day, equivalent to 7.5 microM NO) in wild-type and SAD mice exposed to 46 h of hypoxia (8% oxygen) followed by 2 h of normoxia resulted in 1) reduction of the hypoxia-induced increase in blood neutrophil count, 2) prevention of hypoxia-induced increased IL-6 and IL-1beta levels in bronchoalveolar lavage, 3) reduction of the lung injury induced by hypoxia-reoxygenation, 4) prevention of thrombus formation, and 5) prevention of hypoxia-induced increase of lung matrix metalloproteinase-9 gene expression. These effects provide new insights into the possible use of NO-Alb in the treatment of acute lung injury in SCD.
authors.affiliation: Section of Internal Medicine, Department of Clinical and Experimental Medicine, University of Verona, Italy. lucia.defranceschi@univr.it
authors.forename: Lucia
authors.initials: L
authors.lastname: de Franceschi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Malpeli
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.forename: Anne
authors.initials: A
authors.lastname: Janin
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Muchitsch
authors.forename: Paola
authors.initials: P
authors.lastname: Roncada
authors.forename: Christhope
authors.initials: C
authors.lastname: Leboeuf
authors.forename: Roberto
authors.initials: R
authors.lastname: Corrocher
authors.forename: Yves
authors.initials: Y
authors.lastname: Beuzard
authors.forename: Carlo
authors.initials: C
authors.lastname: Brugnara
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications*; D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004341:Drug Evaluation; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000150:complications*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009603:Nitroso Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects; D011668:Pulmonary Veno-Occlusive Disease / Q000517:prevention & control*; D015427:Reperfusion Injury / Q000150:complications*; D012710:Serum Albumin, Bovine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D009603:Nitroso Compounds; C091665:S-nitrosoalbumin; D012710:Serum Albumin, Bovine; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse