title: Association of Heme Oxygenase 1 with Lung Protection in Malaria-Associated ALI/ARDS.
abstract: Malaria is a serious disease, caused by the parasite of the genusPlasmodium, which was responsible for 440,000 deaths in 2015. Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the main clinical complications in severe malaria. The murine model DBA/2 reproduces the clinical signs of ALI/ARDS in humans, when infected withPlasmodium bergheiANKA. High levels of HO-1 were reported in cases of severe malaria. Our data indicated that the HO-1 mRNA and protein expression are increased in mice that develop malaria-associated ALI/ARDS (MA-ALI/ARDS). Additionally, the hemin, a HO-1 inducing drug, prevented mice from developing MA-ALI/ARDS when administered prior to the development of MA-ALI/ARDS in this model. Also, hemin treatment showed an amelioration of respiratory parameters in mice, high VEGF levels in the sera, and a decrease in vascular permeability in the lung, which are signs of ALI/ARDS. Therefore, the induction of HO-1 before the development of MA-ALI/ARDS could be protective. However, the increased expression of HO-1 on the onset of MA-ALI/ARDS development may represent an effort to revert the phenotype of this syndrome by the host. We therefore confirm that HO-1 inducing drugs could be used for prevention of MA-ALI/ARDS in humans.
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Marcelo L M
authors.initials: ML
authors.lastname: Pereira
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Luana S
authors.initials: LS
authors.lastname: Ortolan
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Sercundes
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Debone
authors.affiliation: Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Oscar
authors.initials: O
authors.lastname: Murillo
authors.affiliation: Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Flávia A
authors.initials: FA
authors.lastname: Lima
authors.affiliation: Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Claudio R F
authors.identifier: 0000-0002-1227-3845
authors.initials: CR
authors.lastname: Marinho
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Sabrina
authors.identifier: 0000-0001-6094-9750
authors.initials: S
authors.lastname: Epiphanio
mesh_terms: D055371:Acute Lung Injury / Q000150:complications / Q000378:metabolism*; D000818:Animals; D002199:Capillary Permeability; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006427:Hemin / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008288:Malaria / Q000150:complications / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008811:Mice, Inbred DBA; D010539:Permeability; D010641:Phenotype; D010962:Plasmodium berghei; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008565:Membrane Proteins; D006427:Hemin; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse