title: Pulmonary and hepatic injury after sub-chronic exposure to sublethal doses of microcystin-LR.
abstract: We had previously shown that microcystin-LR (MCLR) could induce lung and liver inflammation after acute exposure. The biological outcomes following prolonged exposure to MCLR, although more frequent, are still poorly understood. Thus, we aimed to verify whether repeated doses of MCLR could damage lung and liver and evaluate the dose-dependence of the results. Male Swiss mice received 10 intraperitoneal injections (i.p.) of distilled water (60 μL, CTRL) or different doses of MCLR (5 μg/kg, TOX5), 10 μg/kg (TOX10), 15 μg/kg (TOX15) and 20 μg/kg (TOX20) every other day. On the tenth injection respiratory mechanics (lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance) was measured. Lungs and liver were prepared for histology (morphometry and cellularity) and inflammatory mediators (KC and MIP-2) determination. All mechanical parameters and alveolar collapse were significantly higher in TOX5, 10, 15 and 20 than CTRL, but did not differ among them. Lung inflammatory cell content increased dose-dependently in all TOX groups in relation to CTRL, being TOX20 the largest. The production of KC was increased in lung and liver homogenates. MIP-2 increased in the liver of all TOX groups, but in lung homogenates it was significantly higher only in TOX20 group. All TOX mice livers showed steatosis, necrosis, inflammatory foci and a high degree of binucleated hepatocytes. In conclusion, sub-chronic exposure to MCLR damaged lung and liver in all doses, with a more important lung inflammation in TOX20 group.
authors: Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Giovanna Marcella Cavalcante
authors: GM
authors: Carvalho
authors: Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Vinícius Rosa
authors: VR
authors: Oliveira
authors: Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Natália Vasconcelos
authors: NV
authors: Casquilho
authors: Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Andressa Cristine Pereira
authors: AC
authors: Araujo
authors: Laboratory of Ecophysiology and Toxicology of Cyanobacteria, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Raquel Moraes
authors: RM
authors: Soares
authors: Laboratory of Ecophysiology and Toxicology of Cyanobacteria, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Sandra Maria F O
authors: SM
authors: Azevedo
authors: Laboratory of Integrative Histology, Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Karla Maria Pereira
authors: KM
authors: Pires
authors: Laboratory of Integrative Histology, Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Samuel Santos
authors: SS
authors: Valença
authors: Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: walter_zin@hotmail.com.
authors: Walter Araujo
authors: WA
authors: Zin
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D054426:Chemokine CXCL2 / Q000819:agonists / Q000378:metabolism; D018925:Chemokines / Q000819:agonists / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity; D006505:Hepatitis / Q000209:etiology; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008387:Marine Toxins / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D051379:Mice; D052998:Microcystins / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D046931:Microcystis / Q000737:chemistry; D009929:Organ Size / Q000187:drug effects; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D059550:Toxicity Tests, Subchronic
chemical_list: D001427:Bacterial Toxins; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D004791:Enzyme Inhibitors; D008387:Marine Toxins; D052998:Microcystins; C074302:keratinocyte-derived chemokines; D010749:Phosphoprotein Phosphatases; C057862:cyanoginosin LR
keywords: Cyanobacteria; Liver inflammation; Lung injury; Microcystin-LR; Subchronic exposure