Abstract

Background: Neutropenia, which is characterized by a low count of neutrophils, plays a critical role in the pathophysiology of acute respiratory distress syndrome and acute lung injury. It is a commonly expected event in numerous cancer patients who receive chemotherapy. Galantamine is a competitive and reversible cholinesterase inhibitor used in the treatment of Alzheimer's disease and other conditions that cause memory impairment. Recent studies showed that galantamine reduced the severity of local inflammation in animals, inhibited the degree of systemic inflammatory response induced by LPS (lipopolysaccharide), and suppressed TNF-alpha expression in rats with LPS-induced peritonitis. The aim of this study was to elucidate whether galantamine is effective in LPS-induced ALI during neutropenia recovery in a murine model.

Methods: Intraperitoneal cyclophosphamide was given to all mice to induce neutropenia. 2 days after, mice were administered LPS by intratracheal instillation. In the first preventive group, galantamine was given by intraperitoneal injection 30 minutes before LPS instillation. In the second preventive group, in order to examine dose-cumulative effect, galantamine was given twice- 5hours and 30minutes before LPS. In the treatment group, galantamine was given 6 hours after LPS. Mice were sacrificed 24 hours after LPS.

Results: Galantamine ameliorated histopathological changes in LPS-induced lung injury. In prevention 2 group, when galantamine was given twice before LPS instillation had most effect in terms of inflammation attenuation.(figure)

Conclusion: The present study demonstrated that galantamine attenuated LPS-induced lung injury during neutropenia recovery.