Characterization of the biochemical effects of 1-nitronaphthalene in rats using global metabolic profiling by NMR spectroscopy and pattern recognition

Abstract

Metabolic fingerprints, in the form of patterns of high-concentration endogenous metabolites, of 1-nitronaphthalene (NN)-induced lung toxicity have been elucidated in bronchoalveolar lavage fluid (BALF), urine, blood plasma, and intact lung and liver tissue using NMR spectroscopy-based metabolic profiling. A single dose of NN (75 mg kg⁻¹) was administered orally to Sprague–Dawley rats. BALF and lung tissue were obtained 24 h after dosing from these animals and matched control rats post-mortem. High-resolution ¹H-NMR spectroscopy of BALF samples indicated that NN caused increases in concentrations of choline, amino acids (leucine, isoleucine and alanine) and lactate together with decreased concentrations of succinate, citrate, creatine, creatinine and glucose. In addition, the intact lung weights were higher in the NN-treated group (p<0.01), consistent with pulmonary oedema. The NMR-detected perturbations indicated that NN induces a perturbation in energy metabolism in both lung and liver tissue, as well as surfactant production and osmolyte levels in the lungs. As well as reporting the first NMR spectroscopic combined examination of BALF and intact lung, this study indicates that such holistic approaches to investigating mechanisms of lung toxicity may be of value in evaluating disease progression or the effects of therapeutic intervention in pulmonary conditions such as surfactant disorders or asthma.

Keywords: :

• Metabonomics
• metabolomics
• biofluid NMR spectroscopy
• pattern recognition

Acknowledgements

British Gas Group Plc is acknowledged for its financial support to J. A. J. L. G. is a Royal Society University Research Fellow.