title: Ketamine inhibits calcium elevation and hydroxyl radical and nitric oxide production in lipopolysaccharide-stimulated NR8383 alveolar macrophages.
abstract: Macrophages play a critical role in mediating inflammatory processes; activated macrophages respond to endotoxin by releasing pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6. Ketamine, a widely used anesthetic agent, has unequivocally anti-inflammatory effects in vivo and in vitro. However, the detailed mechanisms for the anti-inflammatory effects of ketamine in microglia have not been elucidated yet. This study aimed to evaluate the effects of ketamine on lipopolysaccharide (LPS)-induced nitric oxide (NO), hydroxyl radical (·OH) production, and intracellular calcium accumulation in macrophages. Macrophages were pretreated with ketamine at the concentrations of 10, 100, and 1,000 μM 1 h before LPS stimulation. The production of NO and ·OH in the culture supernatant of macrophages was assayed by Griess Reagent Kit. LPS enhanced NO and ·OH production and provoked a significant intracellular calcium elevation. With the concentrations higher than 100 μM, ketamine inhibited LPS-induced NO and ·OH accumulation and intracellular calcium elevation. However, a low concentration of ketamine (10 μM) did not exert anti-inflammatory effects. These results suggest that intracellular calcium elevation is, at least, partially involved in the inhibitory effect of ketamine.
authors.affiliation: Department of Anesthesiology, The First People's Hospital of Lianyungang City, Lianyungang, Jiangsu Province, People's Republic of China.
authors.forename: Xiaobao
authors.initials: X
authors.lastname: Zhang
authors.forename: Jiying
authors.initials: J
authors.lastname: Feng
authors.forename: Pin
authors.initials: P
authors.lastname: Zhu
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D017665:Hydroxyl Radical / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007649:Ketamine / Q000494:pharmacology*; D008070:Lipopolysaccharides; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000700:Analgesics; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D007649:Ketamine; D002118:Calcium