The prevention of lipopolysaccharide-induced pulmonary vascular injury by pretreatment with cepharanthine in rats.
Cepharanthine, a biscoclaurine alkaloid, has been shown to inhibit leukocyte activation in vitro. To determine whether cepharanthine may be of use in the treatment of acute respiratory distress syndrome (ARDS), we investigated its effect on lipopolysaccharide (LPS)-induced pulmonary vascular injury in rats, in which activated leukocytes have been implicated. Intravenous administration of LPS (5 mg/kg) induced pulmonary vascular injury, as indicated by increases in both the pulmonary vascular permeability and the lung wet/dry weight ratio. LPS-induced pulmonary vascular injury was significantly less in animals given cepharanthine (10 mg/kg) intraperitoneally. Cepharanthine significantly inhibited the LPS-induced increases in plasma tumor necrosis factor-alpha (TNF-alpha) concentrations in vivo and significantly inhibited the production of TNF-alpha by LPS-stimulated monocytes in vitro. Cepharanthine also inhibited the functions of activated neutrophils in vitro such as neutrophil elastase release, oxygen radical generation, and neutrophil aggregation, probably by inhibiting a rise in the intracellular free calcium concentration. These findings suggest that cepharanthine prevents LPS-induced pulmonary vascular injury by inhibiting leukocyte activation.
Murakami
K
K
Department of Laboratory Medicine, Kumamoto University School of Medicine, Kumamoto, Japan.
Okajima
K
K
Uchiba
M
M
D000470:Alkaloids / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D044182:Benzylisoquinolines; D002118:Calcium / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D004926:Escherichia coli; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D052117:Benzodioxoles
D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D044182:Benzylisoquinolines; D002118:Calcium; D007375:Interleukin-1; D019272:Leukocyte Elastase; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C006947:cepharanthine; D052117:Benzodioxoles