Protective effect of luteolin on acute lung injury in sepsis mice

Abstract

Objective To investigate the potential therapeutic effect of luteolin on sepsis-induced ALI and the underlying mechanisms. Methods Total of 50 mice were randomly(random number) divided into five groups: a sham control group, a sepsis-induced ALI group, and three sepsis groups pre-treated with 20, 40, and 80 mg/kg body weight luteolin. Mice in the treatment groups were pre-treated with luteolin at the respective oral dose two days before ALI induction. The lungs were isolated for histopathological examinations, and the bronchoalveolar lavage fluid (BALF) was collected for biochemical analyses. Results Luteolin significantly attenuated sepsis-induced ALI. Additionally, luteolin treatment decreased protein and inflammatory cytokine concentration and the number of infiltrated inflammatory cells in BALF compared with that in the non-treated sepsis mice. Pulmonary myeloperoxidase (MPO) activity was lower in the luteolin-pre-treated sepsis groups than in the sepsis group. The mechanism underlying the protective effect of luteolin on sepsis is related to the up-regulation of certain antioxidation genes, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), superoxide dismutases (SODs), and heme oxygenase 1 (HO-1), and the reduction of inflammatory responses through blockage of the activation of the nuclear factor (NF)-κB pathway. Conclusions Luteolin pre-treatment inhibits sepsis-induced ALI through its anti-inflammatory and antioxidative activity, suggesting that luteolin may be a potential therapeutic agent for sepsis-induced ALI. Key words: Luteolin; Sepsis; COX-2; SODs; iNOS