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Oleic acid induces acute pulmonary injury and inflammation in vivo
Citation:
Bass, V., M. Schladweiler, U. Kodavanti, Andy Ghio, AND M. Madden. Oleic acid induces acute pulmonary injury and inflammation in vivo. Society of Toxicology (SOT) Annual Meeting, San Antonio, TX, March 11 - 15, 2018.
Impact/Purpose:
This project will involve a series of experiments to determine the vascular effects of fatty acids and some mechanisms involved. Initial experiments will focus on oleic acid (as the fatty acid) exposure and the role of iron in the biological responses. The pilot study experiment will determine if the dose of oleic acid induces adequate injury for subsequent more in-depth mechanistic studies. Subsequent study designs will be based on findings from the pilot study (or a second pilot study if the initial design is not adequate to show lung and extrapulmonary damage).
Description:
Oleic acid (OA) is frequently used as a representative fatty acid, and is found in meat-cooking fumes and biodiesel exhaust. Vascular damage and acute lung injury has been observed with OA vascular infusion in models of acute respiratory distress, but it is not yet established whether OA deposited in the lung is able to produce adverse pulmonary and cardiovascular effects associated with exposure to ambient air pollution. We hypothesized that OA via intratracheal (IT) exposure would induce lung injury and alteration to vascular biomarkers, and that these changes could be mitigated by the co-administration of excess iron. Iron has been demonstrated to attenuate lung injury induced by some air pollutants. Sixty-four Wistar Kyoto rats aged 12 weeks were assigned to one of four treatments: vehicle control (0.04% EtOH in saline), OA (20mg/kg), ferric ammonium citrate (FAC) (0.43mg/kg), or OA + FAC (20mg/kg OA + 0.43mg/kg FAC) administered IT (1ml/kg). Plethysmography and collection of tissues, bronchoalveolar lavage fluid (BALF), and blood was performed at 4hr or 24hr after instillation. OA increases enhanced pause (PenH) (an index of air-flow limitation): saline control: 0.66±0.04; OA: 1.5±0.1; OA +FAC: 1.8±0.2. OA increased BALF LDH at 4hr, (saline control: 37.6±1.6 U/L; OA: 59.2±2.2 U/L; OA + FAC:87.6±5.3 U/L). BAL neutrophil count in the lung increased by 20.8±3.8 percent with OA and 27.3±5.5 percent with OA + FAC, relative to the control. Total BALF protein and albumin were significantly higher in OA (at 4 and 24 hr) and were further exacerbated in OA + FAC rats at 4hr. FAC alone did not significantly alter the BALF markers of lung injury and inflammation. Collectively, these data indicate that when given IT, OA induces acute lung injury and inflammation. Rather than mitigating lung damage, when given simultaneously IT excess iron in FAC appears to exacerbate these effects. (Does not reflect official US EPA policy).