Abstract
Background and Objective: Pulmonary diseases are among the leading causes of mortality and disability worldwide and lower respiratory infections ranked as the fourth leading cause of death. This study aimed to the effects of three different doses of endotoxin on lung pathogenicity and selected the dose that induced the highest inflammatory response to investigate inflammation/nitrosative stress axis mediated lung injury. Materials and Methods: The model groups of rats were subjected to a single injection via Intra-Tracheal (IT) instillation of 5, 10 and 15 mg kg(-1) of endotoxin (En) and the control group received a saline injection. All rats were culled 3 days post endotoxin injection. Results: A severe acute lung injury was detected in all three experimental groups as revealed by a sharp increase in blood and/or lung tissue Granulocyte Monocyte-Colony Stimulating Factor (GM-CSF) levels, interleukin-6 (IL-6) and interleukin-17A (IL-17A). The order of potencies of the endotoxin's effects was: En15>En10>En5. En15 also (i) Demonstrated coagulopathy, including increased blood levels of prothrombin time (PT), plasminogen activator inhibitor (PAI-1), activated Partial Thromboplastin Time (APTT) and D-dimer, (ii) Caused >15 fold increase in lung tissue levels of nitrosative stress biomarker, Inducible Nitric Oxide Synthase (iNOS) and (iii) Induced lung tissue damage like a collapse of alveoli and interalveolar septal thickening. Conclusion: These findings demonstrated that endotoxin at 15 mg kg(-1) b.wt., induces after 3 days in rats a profound lung injury associated with the augmentation of the inflammation/iNOS axis, as well as coagulopathy biomarkers. Using this model may be useful for testing agents to treat severe acute lung damage.