title: Oleanolic acid improves pulmonary morphofunctional parameters in experimental sepsis by modulating oxidative and apoptotic processes.
abstract: We compared the effects of oleanolic acid (OA) vs. dexamethasone on lung mechanics and histology, inflammation, and apoptosis in lung and distal organs in experimental sepsis. Seventy-eight BALB/c mice were randomly divided into two groups. Sepsis was induced by cecal ligation and puncture, while the control group underwent sham surgery. 1h after surgery, all animals were further randomized to receive saline (SAL), OA and dexamethasone (DEXA) intraperitoneally. Both OA and DEXA improved lung mechanics and histology, which were associated with fewer lung neutrophils and less cell apoptosis in lung, liver, and kidney than SAL. However, only animals in the DEXA group had lower levels of interleukin (IL)-6 and KC (murine analog of IL-8) in bronchoalveolar lavage fluid than SAL animals. Conversely, OA was associated with lower inducible nitric oxide synthase expression and higher superoxide dismutase than DEXA. In the experimental sepsis model employed herein, OA and DEXA reduced lung damage and distal organ apoptosis through distinct anti-inflammatory mechanisms.
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics (IBCCF), Federal University of Rio de Janeiro (UFRJ), Brazil.
authors.forename: Raquel Souza
authors.initials: RS
authors.lastname: Santos
authors.forename: Pedro Leme
authors.initials: PL
authors.lastname: Silva
authors.forename: Gisele Pena
authors.initials: GP
authors.lastname: de Oliveira
authors.forename: Cintia Lourenço
authors.initials: CL
authors.lastname: Santos
authors.forename: Fernanda Ferreira
authors.initials: FF
authors.lastname: Cruz
authors.forename: Edson Fernandes
authors.initials: EF
authors.lastname: de Assis
authors.forename: Hugo Caire
authors.initials: HC
authors.lastname: de Castro-Faria-Neto
authors.forename: Vera Luiza
authors.initials: VL
authors.lastname: Capelozzi
authors.forename: Marcelo Marcos
authors.initials: MM
authors.lastname: Morales
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelosi
authors.forename: Cerli Rocha
authors.initials: CR
authors.lastname: Gattass
authors.forename: Patricia Rieken Macedo
authors.initials: PR
authors.lastname: Rocco
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009828:Oleanolic Acid / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D018805:Sepsis / Q000150:complications / Q000188:drug therapy; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D009828:Oleanolic Acid; D003907:Dexamethasone; D002374:Catalase; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase
keywords: Chemokine; Cytokines; Dexamethasone; Histology; Lung mechanics; Oxidative stress