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

Abstract

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