Oxidative stress, inflammatory, and immune response after inhalation exposure to biodiesel exhaust.
Kisin-EK; Murray-AR; Tkach-AV; Gavett-SH; Gilmour-MI; Shvedova-AA
Toxicologist 2012 Mar; 126(Suppl 1):527
Biodiesel (BD) is an advanced fuel produced from renewable domestic sources. The broad uses of BD in different industries including mining may lead to potential health effects. We hypothesized that the toxicity of biodiesel exhaust (BDE) is dependent at least on three major mechanisms: direct reactivity of BDE PM electrophiles towards critical biomolecules, induction of robust inflammatory response associated with the nano-sized components of BD PM, and triggering of oxidative stress via depletion of essential antioxidants and activation of oxidative burst in inflammatory cells. In the current study, we evaluated these pathways in BALB/cJ mice 24 hr after 4 weeks of inhalation exposure to BD (0, 50, 150 and 500 microg/m3; 4 hr/day, 5 d/wk, 4 wk). Biomarkers of pulmonary damage (LDH) and inflammation (myeloperoxidase, MPO) were significantly elevated in the lungs from mice exposed to BDE. Additionally, we observed that inhalation exposure caused a significant accumulation of oxidatively modified proteins (carbonyls), increase in 4-hydroxynonenal (4-HNE), reduction of protein thiols, and depletion of antioxidant - gluthatione (GSH). To assess the effects of BDE on pulmonary antigen presenting cells (APC), expression of CD80, CD86, CD40 and MHCII class molecules on lung dendritic cells (DC) was evaluated. BDE altered the phenotype of APC in the lung and facilitated the recruitment of immature DC into the lung tissues. The proliferative response of spleen T cells upon BDE exposure (ex vivo) was increased while no changes were observed in regulatory T cell numbers. Overall, the results show that exposure to BDE induces inflammation and oxidative damage in the lungs and stimulates local and systemic immune responses. Further investigations will compare the relative potency of different blends of BDE against petroleum diesel. (This abstract does not represent US EPA policy.)
Fuels; Fuel-production; Biohazards; Biological-material; Diesel-emissions; Diesel-exhausts; Health-hazards; Hazardous-materials; Toxic-materials; Immune-system; Immune-reaction; Nanotechnology; Oxidative-processes; Electrophysiological-effects; Molecular-biology; Cellular-reactions; Antioxidants; Laboratory-animals; Laboratory-testing; Inhalation-studies; Myeloid-tissue; Pulmonary-function; Peroxidases; Lung-function; Carbonyls; Thiols; Proteins; Lung-tissue; Cellular-function
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California