title: Effects of ketamine, propofol, and ketofol on proinflammatory cytokines and markers of oxidative stress in a rat model of endotoxemia-induced acute lung injury.
abstract: Intravenous lipopolysaccharide (LPS) leads to acute lung injury (ALI) in rats. The purpose of this study was to examine the anti-inflammatory and antioxidant efficacy of ketamine, propofol, and ketofol in a rat model of ALI. We induced ALI in rats via intravenous injection of LPS (15 mg kg(-1)). The animals were randomly separated into five groups: control, LPS only, LPS + ketamine (10 mg·kg(-1)·h(-1)), LPS + propofol (10 mg·kg(-1)·h(-1)), LPS + ketofol (5 mg·kg(-1)·h(-1) ketamine + 5 mg·kg(-1)·h(-1) propofol). LPS resulted in an increase in the release of pro-inflammatory cytokines, mRNA expression related with inflammation, production of nitric oxide, and lipid peroxidation. Ketamine prevented the increase in markers of oxidative stress and inflammation mediators, both in plasma and lung tissue. Propofol decreased the levels of cytokines in plasma and lung tissue, whereas it had no effect on the IL-1-beta level in lung tissue. Ketamine downregulated mediators of lung tissue inflammation and reduced the level of circulating cytokines and protected lung tissue against lipid peroxidation. Ketofol decreased the level of TNF-α and IL-1β in plasma, as well as expression of cyclooxygenase-2 mRNA and the nitrate/nitrite level in lung tissue. The results of this investigation support the hypothesis that ketamine may be effective in preventing ALI.
authors.affiliation: Ankara Numune Training and Research Hospital, Department of Anesthesiology, Ankara, Turkey.
authors.forename: Derya
authors.initials: D
authors.lastname: Gokcinar
authors.forename: Volkan
authors.initials: V
authors.lastname: Ergin
authors.forename: Ahmet
authors.initials: A
authors.lastname: Cumaoglu
authors.forename: Adnan
authors.initials: A
authors.lastname: Menevse
authors.forename: Aysel
authors.initials: A
authors.lastname: Aricioglu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D061605:Administration, Intravenous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004338:Drug Combinations; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D015870:Gene Expression; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007649:Ketamine / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D004338:Drug Combinations; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007649:Ketamine; D051546:Cyclooxygenase 2; D015742:Propofol