Luteolin attenuates acute lung injury in experimental mouse model of sepsis

The present investigation was undertaken to assess the result of pretreatment of luteolin in sepsis-induced acute lung injury in mice and its mechanism of action. Luteolin was administered intraperitoneally one hour before caeca] ligation and puncture (CLP) surgery in mice. Acute lung injury was assessed by estimation of different parameters like lung edema, protein content, cytokines level, oxidative stress, inducible nitric oxide synthase (iNOS), intercellular adhesion molecule (ICAM)-1 expression and histopathology. Pretreatment of mice with luteolin showed decrease lung edema and protein content in tissue and bronchoalveolar lavage fluid (BALF). However, mice pretreated with luteolin showed reduction (p = 0.92) in blood and lung tissue bacterial counts however it was non significant. Further, luteolin showed significant reduction in interleukin (IL)-6 and IL-1 beta in lung tissue which are the proinflammatory cytokines. However, plasma IL-1 beta and tissue tumor necrosis factor (TNF)-alpha level decrease (p = 0.24; p = 0.19) with this pretreatment. Further, ICAM-1 mRNA expression and nuclear factor (NF)-kappa B protein expression were significantly (p < 0.01) decreased in luteolin pretreated septic mice. The lung iNOS level, iNOS mRNA and protein expressions were markedly (p = 0.25; p = 0.50; p = 0.06) altered with luteolin pretreatment, respectively. Also, significant reduction in lipid peroxidation and increase in the activity of antioxidant enzymes like superoxide dismutase (SOD) and catalase was noted with luteolin pretreatment. However, luteolin did not alter (p = 0.36) the non enzymatic antioxidant GSH activity in septic mice. Histopathology of lung tissue showed reduction in lung injury with the luteolin pretreatment in septic mice. The study suggests that luteolin showed attenuation in sepsis-induced acute lung injury in mice through suppression in ICAM-1, NF-kappa B, oxidative stress and partially iNOS pathways.