cyanoginosin-lr and Pneumonia

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.

Topics: Animals; Bacterial Toxins; Chemical and Drug Induced Liver Injury; Chemokine CXCL2; Chemokines; Dose-Response Relationship, Drug; Enzyme Inhibitors; Hepatitis; Injections, Intraperitoneal; Liver; Lung; Male; Marine Toxins; Mice; Microcystins; Microcystis; Organ Size; Phosphoprotein Phosphatases; Pneumonia; Random Allocation; Toxicity Tests, Subchronic

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.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bacterial Toxins; Chemical and Drug Induced Liver Injury; Inflammation Mediators; Liver; Lung; Marine Toxins; Mice; Microcystins; Neutrophil Infiltration; Phosphodiesterase Inhibitors; Phthalic Acids; Phthalimides; Pneumonia; Pulmonary Alveoli; Random Allocation; Sulfonamides

Cyanobacterial blooms and hepatotoxic microcystins (MCs) usually occur in summer, constituting a sanitary and environmental problem in Salto Grande Dam, Argentina. Water sports and recreational activities take place in summer in this lake. We reported an acute case of cyanobacterial poisoning in Salto Grande dam, Argentina, which occurred in January 2007. Accidentally, a young man was immersed in an intense bloom of Microcystis spp. A level of 48.6 μg·L(-1) of microcystin-LR was detected in water samples. Four hours after exposure, the patient showed nausea, abdominal pain and fever. Three days later, dyspnea and respiratory distress were reported. The patient was hospitalized in intensive care and diagnosed with an atypical pneumonia. Finally, a week after the exposure, the patient developed a hepatotoxicosis with a significant increase of hepatic damage biomarkers (ALT, AST and γGT). Complete recovery took place within 20 days. This is the first study to show an acute intoxication with microcystin-producing cyanobacteria blooms in recreational water.

Topics: Argentina; Bacterial Toxins; Biomarkers; Harmful Algal Bloom; Humans; Liver Diseases; Liver Function Tests; Male; Marine Toxins; Microcystins; Microcystis; Pneumonia; Recreation; Water Microbiology; Young Adult

The treatment of microcystin-LR (MCYST-LR)-induced lung inflammation has never been reported. Hence, LASSBio 596, an anti-inflammatory drug candidate, designed as symbiotic agent that modulates TNF-alpha levels and inhibits phosphodiesterase types 4 and 5, or dexamethasone were tested in this condition. Swiss mice were intraperitoneally (i.p.) injected with 60 microl of saline (CTRL) or a sub-lethal dose of MCYST-LR (40 micrg/kg). 6 h later they were treated (i.p.) with saline (TOX), LASSBio 596 (10 mg/kg, L596), or dexamethasone (1 mg/kg, 0.1 mL, DEXA). 8 h after MCYST-LR injection, pulmonary mechanics were determined, and lungs and livers prepared for histopathology, biochemical analysis and quantification of MCYST-LR. TOX showed significantly higher lung impedance than CTRL and L596, which were similar. DEXA could only partially block the mechanical alterations. In both TOX and DEXA alveolar collapse and inflammatory cell influx were higher than in CTRL and L596, being LASSBio 596 more effective than dexamethasone. TOX showed oxidative stress that was not present in CTRL and L596, while DEXA was partially efficient. MCYST-LR was detected in the livers of all mice receiving MCYST-LR and no recovery was apparent. In conclusion, LASSBio 596 was more efficient than dexamethasone in reducing the pulmonary functional impairment induced by MCYST-LR.

Topics: Animals; Anti-Inflammatory Agents; Bacterial Toxins; Chemical and Drug Induced Liver Injury; Dexamethasone; Male; Marine Toxins; Mice; Microcystins; Phthalic Acids; Phthalimides; Pneumonia; Sulfonamides