Bosentan reduces oxidative burst in acid aspiration-induced lung injury in rats.
BACKGROUND
Acid aspiration induces lung injury by causing an intense inflammatory reaction. Neutrophils are attracted by various cytokines, such as TNFbeta, and release reactive oxygen species, which then cause acute lung injury. Endothelin antagonists, such as bosentan, have been found to possess anti-inflammatory properties.


METHODS
We performed a prospective, randomised, controlled study to evaluate the effects of bosentan in a rat model of acid-induced lung injury. Sprague-Dawley rats underwent sevoflurane anaesthesia; lung injury was then induced by instillation of 1.2mL/kg, 0.1M hydrochloric acid. The lungs were ventilated for 6h and then randomised into three groups: bosentan 30mg/kg body weight, 90mg/kg body weight or sodium chloride, each applied immediately after acid aspiration via a gastric tube.


RESULTS
After induction of acute lung inflammation, the production of reactive oxygen species by PMN following stimulation with FMLP increased significantly. Comparison of pre-treatment and post-treatment in the 90mg/kg bosentan treatment group did not show a significant increase of reactive oxygen species following stimulation with FMLP. A comparison of the absolute difference of the MESF demonstrated a significant difference between the control group and the group treated with 90mg/kg bosentan.


CONCLUSIONS
Bosentan administration at 90mg/kg body weight reduced the release of reactive oxygen species after 360min in acid aspiration-induced lung injury in rats.
Trabold
Benedikt
B
Department of Anaesthesiology, University Medical Center, Regensburg, Germany. benedikt.trabold@klinik.uni-regensburg.de
Pawlik
Michael
M
Nietsch
Renata
R
Bitzinger
Diane I
DI
Gruber
Michael
M
Ittner
Karl-Peter
KP
Lubnow
Matthias
M
D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000077300:Bosentan; D006851:Hydrochloric Acid / Q000633:toxicity; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011015:Pneumonia, Aspiration / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016897:Respiratory Burst / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D013449:Sulfonamides; D000077300:Bosentan; D006851:Hydrochloric Acid