Memantine, A NMDA Receptor Inhibitor Attenuate Lipopolysaccharide-Induced Lung Inflammation and Oxidative Damage in Mice

Background The anti-oxidative and anti-inflammatory effect of memantine (an N-methyl-D-aspartate receptor inhibitor) has been shown. Therefore, the present study aimed to evaluate the preventive effects of memantine against lipopolysaccharide (LPS)-induced sub-acute lung injury in mice. Methods Male C57BL/6 mice (n=30) were randomized in five groups as follows: (1) control (saline containing 10% DMSO); (2) LPS (5 mg/kg, intraperitoneally); and (3, 4, and 5) LPS 5 mg/kg + memantine 5, 10, 20 mg/kg, respectively. Memantine (dissolved in 10% DMSO) was administrated orally three days before the LPS injection and continued for three days after injury induction. Finally, the levels of markers of oxidative stress, malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD), interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and nitric oxide (NO), were measured and histopathological changes in the lung tissue were assessed. Results Lipopolysaccharide (LPS) administration increased the TNF-α, IL-1β, NO, and MDA, levels, while decreasing the lung tissues activity of CAT (P< 0.05) and SOD (P< 0.001) and caused lung pathological damages. Memantine 20 mg/kg, alleviated LPS-induced injury score, reduced the lung tissue levels of TNF-α, IL-1β, MDA, and NO, and restored CAT activity (P< 0.05, P< 0.01). Conclusions LPS-triggered elevation of lung injury markers including histopathological changes, inflammatory cytokines, and oxidative damage. All pathological changes were suppressed by memantine.