Can LASSBio 596 and dexamethasone treat acute lung and liver inflammation induced by microcystin-LR?
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.
Carvalho
Giovanna M C
GM
Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil.
Oliveira
Vinícius R
VR
Soares
Raquel M
RM
Azevedo
Sandra M F O
SM
Lima
Lidia M
LM
Barreiro
Eliezer J
EJ
Valença
Samuel S
SS
Saldiva
Paulo H N
PH
Faffe
Débora S
DS
Zin
Walter A
WA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000473:pathology; D003907:Dexamethasone / Q000627:therapeutic use*; D008297:Male; D008387:Marine Toxins; D051379:Mice; D052998:Microcystins / Q000633:toxicity*; D010795:Phthalic Acids; D010797:Phthalimides / Q000627:therapeutic use*; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides
D000893:Anti-Inflammatory Agents; D001427:Bacterial Toxins; C514420:LASSBIO596; D008387:Marine Toxins; D052998:Microcystins; D010795:Phthalic Acids; D010797:Phthalimides; D013449:Sulfonamides; D003907:Dexamethasone; C057862:cyanoginosin LR