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.

Galantamine protects against hydrochloric acid aspirationinduced acute respiratory distress syndrome in rabbits

“…In the present study, it was shown that GAL suppressed acute inflammatory response during the second phase of acute of acid aspirationinduced ARDS, and also suppressed the inflammation mediator HMGB1, but had no appreciable effect on serum concentrations of corticosterone. Notwithstanding the differences in animal models used, these results are in agreement with the report that GAL protects rats from LPS-provoked ALI [15].…”

Cholinergic modulation of the immune system presents new approaches for treating inflammation

“…Administration of a higher dose of xanomeline 20 h before surgery actually decreased survival, suggesting possible over activation of the anti-inflammatory circuit. Pretreatment with galantamine, a reversible cholinesterase inhibitor, increased survival in LPS-treated mice and reduced acute lung injury (Li et al, 2016; Pavlov et al, 2009). The effects of galantamine to increase survival and reduce serum TNF in LPS-treated mice were attributed to central inhibition of acetylcholinesterase and activation of the vagal anti-inflammatory pathway via stimulation of central muscarinic receptors (Pavlov et al, 2009).…”

Antioxidant and Anti-Inflammatory Effects of Rhamnazin on Lipopolysaccharide-Induced Acute Lung Injury and Inflammation in Rats

“…Histopathological examination was performed as described by Li et al (2016). The upper lobes of the right lungs were excised from all the six experimental groups.…”