The protective effect of Trillin LPS-induced acute lung injury by the regulations of inflammation and oxidative state

Abstract

Inflammation response and oxidative stress have been reported to be involved in the pathogenesis of acute lung injury (ALI). Accordingly, anti-inflammatory treatment is proposed to be a possible efficient therapeutic strategy for ALI. The purpose of our present study was to evaluate the anti-inflammatory efficacy of trillin (Tr) on ALI induced by lipopolysaccharide (LPS) in mice and explore the underlying mechanism. BALB/c mice received Tr (50, 100 mg/kg) intraperitoneally 1 h prior to the intratracheal instillation of lipopolysaccharide (LPS) challenge. Pretreatment with Tr at the dose of 50, 100 mg/kg markedly ameliorated lung wet-to-dry weight (W/D) ratio, myeloperoxidase (MPO) activity and pulmonary histopathological conditions. In addition, the protective efficacy of Tr might be attributed to the down-regulations of neutrophil infiltration, malondialdehyde (MDA), inflammatory cytokines and the up-regulations of super-oxide dismutase (SOD), catalase(CAT), glutathione(GSH), Glutathione Peroxidase(GSH-Px) in bronchoalveolar lavage fluid (BALF). Meanwhile, our study revealed some correlations between (NF-E2-related factor 2) Nrf2/heme oxygenase (HO)-1/nuclear factor-kappa B (NF-κB) pathways and the beneficial effect of Tr, as evidenced by the significant up-regulations of HO-1 and Nrf2 protein expressions as well as the down-regulations of p-NF-κB and p-inhibitor of NF-κB (IκB) in lung tissues. Taken together, our results indicated that Tr exhibited protective effect on LPS-induced ALI by the regulations of related inflammatory events via the activations of Nrf2, HO-1 and NF-κB pathway. The current study indicated that Tr could be a potentially effective candidate medicine for the treatment of ALI.

Keywords: Acute lung injury; HO-1; NF-κB; Nrf2; Trillin.