title: Galantamine protects against lipopolysaccharide-induced acute lung injury in rats.
abstract: Lipopolysaccharide (LPS)-induced endotoxemia triggers the secretion of proinflammatory cytokines and can cause acute lung injury (ALI). The high mobility group box 1 (HMGB1) protein plays an important role as a late mediator of sepsis and ALI. Galantamine (GAL) is a central acetylcholinesterase inhibitor that inhibits the expression of HMGB1. This study evaluated the effects of GAL by measuring levels of inflammatory mediators and observing histopathological features associated with LPS-induced ALI. Sixty 8-10 week old male Sprague-Dawley rats (200-240 g) were randomized into three groups as follows: control group, LPS group (7.5 mg/kg LPS), and LPS+GAL group (5 mg/kg GAL before LPS administration). Histopathological examination of lung specimens obtained 12 h after LPS administration was performed to analyze changes in wet-to-dry (W/D) weight ratio, myeloperoxidase (MPO) activity, and HMGB1 expression level. Additionally, plasma concentrations of tumor necrosis factor-α, interleukin-6, and HMGB1 were measured using an enzyme-linked immunosorbent assay at 0 (baseline), 3, 6, 9, and 12 h after LPS administration. Mortality in the three groups was recorded at 72 h. LPS-induced ALI was characterized by distortion of pulmonary architecture and elevation of MPO activity, W/D weight ratio, and levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, and HMGB1. Pretreatment with GAL significantly reduced the LPS-induced lung pathological changes, W/D weight ratio, levels of pro-inflammatory cytokines and MPO activity (ANOVA). Moreover, GAL treatment significantly decreased the mortality rate (ANOVA). In conclusion, we demonstrated that GAL exerted a protective effect on LPS-induced ALI in rats.
authors.affiliation: Renmin Hospital, Department of Critical Care Medicine, Wuhan University, Wuhan, Hubei Province, China.
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.affiliation: Renmin Hospital, Department of Critical Care Medicine, Wuhan University, Wuhan, Hubei Province, China.
authors.forename: C L
authors.initials: CL
authors.lastname: Zhou
authors.affiliation: Renmin Hospital, Department of Critical Care Medicine, Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Q S
authors.initials: QS
authors.lastname: Zhou
authors.affiliation: Renmin Hospital, Department of Critical Care Medicine, Wuhan University, Wuhan, Hubei Province, China.
authors.forename: H D
authors.initials: HD
authors.lastname: Zou
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005702:Galantamine / Q000627:therapeutic use*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009026:Mortality; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D020011:Protective Agents / Q000627:therapeutic use; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D002800:Cholinesterase Inhibitors; D024243:HMGB1 Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D005702:Galantamine; D009195:Peroxidase