TY - JOUR
T1 - Luteolin reduces lipopolysaccharide-induced lethal toxicity and expression of proinflammatory molecules in mice
AU - Kotanidou, Anastasia
AU - Xagorari, Angeliki
AU - Bagli, Eleni
AU - Kitsanta, Panagiota
AU - Fotsis, Theodore
AU - Papapetropoulos, Andreas
AU - Roussos, Charis
PY - 2002/3/15
Y1 - 2002/3/15
N2 - Luteolin is a flavonoid that has been shown to reduce proinflammatory molecule expression in vitro. In the present study, we have tested the ability of luteolin to inhibit lipopolysaccharide (LPS)-induced lethal toxicity and proinflammatory molecule expression in vivo. Mice receiving LPS (Salmonella enteriditis LPS, 32 mg/kg, intraperitoneally) exhibited high mortality with only 4.1% of the animals surviving seven days after the LPS challenge. On the contrary, mice that had received luteolin (0.2 mg/kg, intraperitoneally) before LPS showed an increased survival rate with 48% remaining alive on Day 7. To investigate the mechanism by which luteolin affords protection against LPS toxicity we measured intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α) production in response to LPS in the presence or absence of luteolin pretreatment. Treatment of animals with LPS increased serum TNF-α levels in a time-dependent manner. The increase in peak serum TNF-α levels was sensitive to luteolin pretreatment. Luteolin pretreatment also reduced LPS-stimulated ICAM-1 expression in the liver and abolished leukocyte infiltration in the liver and lung. We conclude that luteolin protects against LPS-induced lethal toxicity, possibly by inhibiting proinflammatory molecule (TNF-α ICAM-1) expression in vivo and reducing leukocyte infiltration in tissues.
AB - Luteolin is a flavonoid that has been shown to reduce proinflammatory molecule expression in vitro. In the present study, we have tested the ability of luteolin to inhibit lipopolysaccharide (LPS)-induced lethal toxicity and proinflammatory molecule expression in vivo. Mice receiving LPS (Salmonella enteriditis LPS, 32 mg/kg, intraperitoneally) exhibited high mortality with only 4.1% of the animals surviving seven days after the LPS challenge. On the contrary, mice that had received luteolin (0.2 mg/kg, intraperitoneally) before LPS showed an increased survival rate with 48% remaining alive on Day 7. To investigate the mechanism by which luteolin affords protection against LPS toxicity we measured intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α) production in response to LPS in the presence or absence of luteolin pretreatment. Treatment of animals with LPS increased serum TNF-α levels in a time-dependent manner. The increase in peak serum TNF-α levels was sensitive to luteolin pretreatment. Luteolin pretreatment also reduced LPS-stimulated ICAM-1 expression in the liver and abolished leukocyte infiltration in the liver and lung. We conclude that luteolin protects against LPS-induced lethal toxicity, possibly by inhibiting proinflammatory molecule (TNF-α ICAM-1) expression in vivo and reducing leukocyte infiltration in tissues.
KW - Intercellular adhesion molecule
KW - Lipopolysaccharide
KW - Luteolin
KW - Sepsis
KW - Tumor necrosis factor-α
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U2 - 10.1164/ajrccm.165.6.2101049
DO - 10.1164/ajrccm.165.6.2101049
M3 - Article
C2 - 11897650
AN - SCOPUS:0037086366
SN - 1073-449X
VL - 165
SP - 818
EP - 823
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 6
ER -