title: LASSBio 596 per os avoids pulmonary and hepatic inflammation induced by microcystin-LR.
abstract: Cyanobacterial blooms that generate microcystins (MCYSTs) are increasingly recognized as an important health problem in aquatic ecosystems. We have previously reported the impairment of pulmonary structure and function by microcystin-LR (MCYST-LR) exposure as well as the pulmonary improvement by intraperitoneally injected (i.p.) LASSBio 596. In the present study, we aimed to evaluate the usefulness of LASSBio 596 per os on the treatment of pulmonary and hepatic injuries induced by MCYST-LR. Swiss mice received an intraperitoneal injection of 40 μl of saline (CTRL) or a sub-lethal dose of MCYST-LR (40 μg/kg). After 6 h the animals received either saline (TOX and CTRL groups) or LASSBio 596 (50 mg/kg, LASS group) by gavage. Eight hours after the first instillation, lung impedance (static elastance, elastic component of viscoelasticity and resistive, viscoelastic and total pressures) was determined by the end-inflation occlusion method. Left lung and liver were prepared for histology. In lung and hepatic homogenates MCYST-LR, TNF-α, IL-1β and IL-6 were determined by ELISA. LASSBio 596 per os (LASS mice) kept all lung mechanical parameters, polymorphonuclear (PMN) cells, pro-inflammatory mediators, and alveolar collapse similar to control mice (CTRL), whereas in TOX these findings were higher than CTRL. Likewise, liver structural deterioration (hepatocytes inflammation, necrosis and steatosis) and inflammatory process (high levels of pro-inflammatory mediators) were less evident in the LASS than TOX group. LASS and CTRL did not differ in any parameters studied. In conclusion, orally administered LASSBio 596 prevented lung and hepatic inflammation and completely blocked pulmonary functional and morphological changes induced by MCYST-LR.
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Natália V
authors.initials: NV
authors.lastname: Casquilho
authors.forename: Giovanna M C
authors.initials: GM
authors.lastname: Carvalho
authors.forename: João L C R
authors.initials: JL
authors.lastname: Alves
authors.forename: Mariana N
authors.initials: MN
authors.lastname: Machado
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Soares
authors.forename: Sandra M F O
authors.initials: SM
authors.lastname: Azevedo
authors.forename: Lidia M
authors.initials: LM
authors.lastname: Lima
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Valença
authors.forename: Alysson R
authors.initials: AR
authors.lastname: Carvalho
authors.forename: Débora S
authors.initials: DS
authors.lastname: Faffe
authors.forename: Walter A
authors.initials: WA
authors.lastname: Zin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000627:therapeutic use; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008387:Marine Toxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D051379:Mice; D052998:Microcystins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D020556:Neutrophil Infiltration / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D010795:Phthalic Acids; D010797:Phthalimides / Q000008:administration & dosage* / Q000627:therapeutic use; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011897:Random Allocation; D013449:Sulfonamides
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001427:Bacterial Toxins; D018836:Inflammation Mediators; C514420:LASSBIO596; D008387:Marine Toxins; D052998:Microcystins; D010726:Phosphodiesterase Inhibitors; D010795:Phthalic Acids; D010797:Phthalimides; D013449:Sulfonamides; C057862:cyanoginosin LR