Simvastatin pretreatment prevents ambient particle-induced lung injury in mice

Abstract

Air particulate pollution negatively affects the health of the population exposed, being the lung the main target organ. Simvastatin (SV) is widely used for the prevention and risk reduction of coronary disease. Its pleiotropic effects may provide benefit for lung diseases. Here, we investigated the preventive effect of simvastatin pretreatment on acute intranasal exposure to ROFA (Residual Oil Fly Ash), and UAP (Urban Air Particle from Buenos Aires). Male BALB/c mice were randomized in two groups to receive either saline (control, C) solution or SV (1 mg/kg bw /day; ip) for 14 days. After SV treatment, ROFA or UAP (1 mg/kg bw) or saline were intranasally delivered for 24 hours generating 4 subgroups for the ROFA experiment (C, SV, ROFA and SV+ROFA) and 3 subgroups for the UAP experiment (C, SV, UAP and SV+UAP). Biomarkers of lung injury were examined in BAL cells evaluating total cell number (TCN), cell differential (CD) and superoxide anion generation (O2-), in lung homogenates assessing superoxide dismutase activity (SOD) and tumor necrosis factor α (TNFα); and in blood samples determining interleukin 6 (IL-6) production. ROFA and UAP produced an acute pulmonary injury, characterized by an increase in BAL, TCN and neutrophilic inflammatory influx, a rise in O2- generation, and production of the proinflammatory TNFα cytokine. SV pretreatment had no significant effect per se on any of these biomarkers but prevented the pulmonary cytotoxicity and inflammation induced by ROFA and UAP. Our results encourage further studies to determine the preventive effects on lung injury induced by air pollutants.

Recent Advances in Particulate Matter and Nanoparticle Toxicology: A Review of theIn VivoandIn VitroStudies

“…Moreover, they have been reported to have potential benefits for a variety of other cardiovascular and noncardiovascular diseases, including cancer, respiratory and neurological disorders [46, 47]. Interestingly, Ferraro and coworkers [48] reported that residual oil fly ash (ROFA) and Urban Air Particle (UAP) from Buenos Aires produced an acute pulmonary injury in mice, characterized by a neutrophilic inflammation, a rise in O 2 − generation, and production of the proinflammatory tumour necrosis alpha (TNF α ) cytokine. Simvastatin pretreatment had no significant effect per se on any of these biomarkers but prevented the pulmonary cytotoxicity and inflammation induced by ROFA and UAP.…”

Ambient Fine Particulate Matter Induces Apoptosis of Endothelial Progenitor Cells Through Reactive Oxygen Species Formation

“…PM was dispersed in solution by ultrasonication in endotoxin-free PBS for 30 min at a concentration of 0.5 µg/µl [15]. Each mouse was treated with 10 ug PM three times per week for 1 month via intranasal instillation that has been widely used and validated as described [16,17,18,19]. Endotoxin-free PBS was used as control.…”

Mechanisms of Action and Efficacy of Statins against Influenza

“…Gower and Graham in 2001 tested lovastatin against the respiratory syncytial virus and proposed lovastatin as an antiviral agent that controls the RhoA membrane localization and affects virus replication [48]. Jacobson et al [49] confirmed significant protection by simvastatin on LPS-induced lung vascular inflammation and implicated a potential role for statins in the management of acute lung injury; however, Ferraro et al [50] adverted to nonsignificant effect of simvastatin on inflammatory biomarkers in lung injuries. Nevertheless, Haidari et al [40], who examined atorvastatin on C57BL/6 mice infected with H3N2 and H1N1, showed reduced lung virus titers and mortality rates.…”