Am. J. Respir. Crit. Care Med.,
Volume 161, Number 1, January 2000, 57-63
The Prevention of Lipopolysaccharide-induced
Pulmonary Vascular Injury by Pretreatment with
Cepharanthine in Rats
KAZUNORI
MURAKAMI,
KENJI
OKAJIMA,
and
MITSUHIRO
UCHIBA
Department of Laboratory Medicine, Kumamoto University School of Medicine, Kumamoto, Japan
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-
(TNF-) concentrations in vivo and significantly inhibited the production of TNF- 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, Okajima K, Uchiba M. The
prevention of lipopolysaccharide-induced pulmonary vascular injury by pretreatment with
cepharanthine in rats.
