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Time course for inhibition of lipopolysaccharide-induced lung injury by genistein: Relationship to alteration in nuclear factor-κB activity and inflammatory agents

Title
Time course for inhibition of lipopolysaccharide-induced lung injury by genistein: Relationship to alteration in nuclear factor-κB activity and inflammatory agents
Authors
Kang J.L.Lee H.W.Lee H.S.Pack I.S.Castranova V.Koh Y.
Ewha Authors
이지희
SCOPUS Author ID
이지희scopus
Issue Date
2003
Journal Title
Critical Care Medicine
ISSN
0090-3493JCR Link
Citation
vol. 31, no. 2, pp. 517 - 524
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Objective: This study determined the time course for inhibition of lipopolysaccharide-induced acute lung injury following a single dose of genistein. In addition, the study investigated whether a multiple dosing schedule with genistein retained the inhibitory effects on acute lung injury, nuclear factor-κB activation, and production of nuclear factor-κB-dependent inflammatory agents, such as matrix metalloproteinase-9 and nitric oxide. Design: Prospective, randomized, laboratory study. Setting: Experimental laboratory at a university. Subjects: Rats weighing 280-300 g. Interventions: Saline or lipopolysaccharide (6 mg/kg of body weight) administered intratracheally with a single dose of genistein (50 mg/kg) or a multiple dosing schedule with genistein (16 mg/kg every 6 hrs for 2 days with lipopolysaccharide treatment at 24 hrs after the first administration of genistein). Measurements and Main Results: A 2-hr pretreatment with genistein (a single dose) inhibited biochemical lung injury variables as well as neutrophil infiltration with a maximal inhibition at 4 hrs after lipopolysaccharide treatment. These inhibitory effects of genistein declined with time and were no longer significant by 14-24 hrs after lipopolysaccharide treatment. The multiple dosing schedule with genistein retained significant inhibitory effects on biochemical lung injury variables and the number of neutrophils in the bronchoalveolar lavage fluid at 24 hrs after lipopolysaccharide treatment compared with a single pretreatment with genistein. The multiple dosing schedule with genistein also enhanced the inhibition of induced nuclear factor-κB activity as well as matrix metalloproteinase-9 activity and nitric oxide production at 24 hrs after lipopolysaccharide treatment. Conclusions: This study reports the time course of the inhibitory effects of a single genistein pretreatment on acute lung injury with the maximal effects at 4 hrs after lipopolysaccharide treatment. However, a multiple dosing schedule with genistein retained the inhibitory effect on acute lung injury at 24 hrs after lipopolysaccharide treatment. The mechanisms by which genistein exerts an inhibitory effect on acute lung injury may involve the suppression of nuclear factor-βB activation, matrix metalloproteinase-9 activity, and NO production.
DOI
10.1097/01.CCM.0000049941.84695.BA
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의학전문대학원 > 의학과 > Journal papers
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