Luteolin reduces lipopolysaccharide-induced lethal toxicity and expression of proinflammatory molecules in mice.
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-alpha (TNF-alpha) production in response to LPS in the presence or absence of luteolin pretreatment. Treatment of animals with LPS increased serum TNF-alpha levels in a time-dependent manner. The increase in peak serum TNF-alpha 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-alpha, ICAM-1) expression in vivo and reducing leukocyte infiltration in tissues.
Kotanidou
Anastasia
A
George P. Livanos Laboratory, Evangelismos Hospital, Department of Critical Care and Pulmonary Services, University of Athens, Athens, Greece.
Xagorari
Angeliki
A
Bagli
Eleni
E
Kitsanta
Panagiota
P
Fotsis
Theodore
T
Papapetropoulos
Andreas
A
Roussos
Charis
C
D000704:Analysis of Variance; D000818:Animals; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000187:drug effects*; D015850:Interleukin-6 / Q000097:blood; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D047311:Luteolin; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism
D005419:Flavonoids; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D047311:Luteolin