Effect of atorvastatin on lipopolysaccharide-induced lung inflammation and hypoxia in mice; modulation of HIF-1α, CINC and MIP-2.

Abstract

Background: Acute lung injury is a crucial pathological state, particularly in some severe infectious respiratory illnesses, distinguished by acute inflammation, pulmonary edema, hypoxia, and neutrophil recruitment. Cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2) play a vital role in neutrophil recruitment.

Objective: Here, we validated the potential repressing effect of atorvastatin on acute lung injury induced by lipopolysaccharide (LPS) in mice.

Materials and methods: Mice were injected with LPS (250 μg/kg; i.p.) daily for 7 days, and atorvastatin (25 and 50 mg/kg; orally) daily along with LPS.

Results: Atorvastatin ameliorated oxidative stress as evidenced by increased reduced glutathione (GSH) and nuclear factor-erythroid 2 related factor 2 (Nrf2) levels and decreased malondialdehyde (MDA) levels. Additionally, it lessened inflammatory biomarkers including tumor necrosis factor-alpha (TNF-α), mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), CINC, and MIP-2, as well as hypoxia biomarker hypoxia-inducible factor-1α (HIF-1α). Moreover, atorvastatin slowed the progression of lung tissue histological lesions.

Conclusion: Collectively, the present study suggests that, atorvastatin effectively protects against LPS-induced acute lung injury through inhibition of oxidative stress, inflammation, hypoxia, and neutrophil recruitment.