Protective Effects of Nerolidol on Thrombotic Events, Systemic Inflammation, Oxidative Stress, and DNA Damage...

Background/Objectives: Inhalation of environmental particulate air pollution has been reported to cause pulmonary and systemic events including coagulation disturbances, systemic inflammation, and oxidative stress. Nerolidol, a naturally occurring sesquiterpene alcohol, has effective antioxidant and anti-inflammatory effects. Hence, the aim in the present investigation was to evaluate the potential ameliorative effects of nerolidol on the coagulation and systemic actions induced by pulmonary exposure to diesel exhaust particles (DEPs). Methods: Nerolidol (100 mg/kg) was given to mice by oral gavage one hour before the intratracheal instillation of DEPs (0.5 mg/kg), and 24 h later various markers of coagulation and systemic toxicity were evaluated. Results: Nerolidol treatment significantly abrogated DEP-induced platelet aggregation in vivo and in vitro. Nerolidol has also prevented the shortening of the prothrombin time and activated plasma thromboplastin time triggered by DEP exposure. Likewise, while the concentrations of fibrinogen and plasminogen activator inhibitor-1 were increased by DEP administration, that of tissue plasminogen activator was significantly decreased. These effects were abolished in the group of mice concomitantly treated with nerolidol and DEP. Moreover, plasma markers of inflammation, oxidative stress, and endothelial dysfunction which were significantly increased in the DEP-treated group, returned to control levels in the nerolidol + DEP group. Nerolidol treatment significantly ameliorated the increase in the concentrations of hypoxia-inducible factor 1α, galectin-3, and neutrophil gelatinase-associated lipocalin induced by pulmonary exposure to DEP. The co-administration of nerolidol + DEPs significantly mitigated the increase in markers of oxidative DNA damage, 8-hydroxy-2-deoxyguanosine, and apoptosis, cleaved-caspase-3, induced by DEP. Conclusions: Collectively, our data demonstrate that nerolidol exert significant ameliorative actions against DEP-induced thrombotic events, endothelial dysfunction, systemic inflammation, oxidative stress, DNA damage, and apoptosis. Pending further pharmacological and toxicological studies, nerolidol could be a promising agent to alleviate the toxicity of inhaled DEPs and other pollutant particles.