Metabonomics for discovering biomarkers of hepatotoxicity and nephrotoxicity

Abstract

Metabonomics has played increasingly important roles in pharmaceutical research and development. Safety assessment of drugs is a key stage in drug development and one which represents a significant attritional hurdle. However, characterization of the molecular mechanisms of drug toxicity still remains an enormous challenge. Recent advancements in 'omics' sciences, and in particular metabonomics, has enabled some elucidation or insights into toxicological sequelae. Metabonomics is a global metabolic profiling framework which utilizes high resolution analytics together with chemometric statistical tools to derive an integrated picture of both endogenous and xenobiotic metabolism. Hepatotoxicity and nephrotoxicity are major reasons that drugs are withdrawn post-market, and hence it is of major concern to both the Food and Drug Administration and pharmaceutical companies. There is a strong need to develop reliable biomarkers that can accurately predict toxicity in the drug discovery and development process and are translatable to the clinic. A deeper understanding of global perturbations in biochemical pathways and useful biomarkers could provide valuable insights about mechanisms of toxicity. This review summarizes some current progress in the application of metabonomic in understanding drug-induced hepatotoxicity and nephrotoxicity, with an emphasis on identifying early toxicity biomarkers.