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Metabolomics in Lung Inflammation: A High Resolution ¹H NMR Study of Mice Exposed to Silica Dust .

Citation

Hu JZ, DN Rommereim, KR Minard, A Woodstock, BJ Harrer, RA Wind, RP Phipps, and PJ Sime.2008."Metabolomics in Lung Inflammation: A High Resolution ¹H NMR Study of Mice Exposed to Silica Dust ."Toxicology Mechanisms and Methods 18(5):385-398. doi:10.1080/15376510701611032

Abstract

First ¹H NMR metabolomics studies on excised lungs and bronchoalveolar lavage fluids (BALF) from mice exposed to crystalline silica are reported. High resolution ¹H NMR metabolic profiling on intact excised lungs is carried out using slow magic angle sample spinning (slow-MAS) ¹H PASS (phase altered spinning sidebands) at a sample spinning rate of 80 Hz while metabolic profiling on BALF is carried out using fast magic angle spinning at 2kHz. Major findings are that the relative concentrations of choline, phosphocholine (PC) and glycerophosphocholine(GPC) are significantly increased in silica exposed mice versus sham controls, indicating an altered membrane choline phospholipids metabolism (MCPM) during lung inflammation. The relative concentrations of glycogen/glucose, lactate and creatine are also increased in mice exposed to silica dusts, suggesting that the cellular energy pathways are affected by silica dust exposure. Elevated levels of Glycine, lysine, glutamate and proline are also fund increased in exposed mice suggesting the activation of a collagen pathway. Overall, metabolic profiles in the lungs of mice exposed to silica dusts are found to be spatially heterogeneous consistent with regional inflammation revealed by in vivo magnetic resonance imaging (MRI).