Tissue-Targeted Metabonomics: Metabolic Profiling by Microdialysis and NMR Spectroscopy

Abstract

This research offers an alternative approach to the study of tissue-specific metabolism by metabonomics, called tissue-targeted metabonomics. Microdialysis sampling was used to sample small endogenous metabolites in tissue extracellular fluid. Samples were then analyzed by proton nuclear magnetic resonance spectroscopy. The research explored analytical and biological considerations for this method. Data treatment, including integration of the NMR spectra and normalization to standards, was optimized for different dialysate types. Time trends in the basal metabolism of liver and heart tissues were described, as were the metabolic effects of anesthesia, circadian rhythms and animal activity. After the method was developed and basal metabolism was adequately characterized, tissue-targeted metabonomics was used to study oxidative stress, induced locally by perfusing doxorubicin through a probe in the liver. Results indicated a localized metabolic response to the doxorubicin dose in awake rats, illustrating the potential of tissue-targeted metabonomics to monitor localized metabolic changes for many applications.