Biomaterial Database

Metabolic profiling as a tool for understanding mechanisms of toxicity. 2008

Christopher J Clarke, and John N Haselden

Novartis Pharma AG, Basel, Switzerland. christopher.clarke@novartis.com

Metabolic profiling (metabolomics/metabonomics) is the measurement in biological systems of the complement of low-molecular-weight metabolites and their intermediates that reflects the dynamic response to genetic modification and physiological, pathophysiological, and/or developmental stimuli. The measurement and interpretation of the endogenous metabolite profile from a biological sample (typically urine, serum, or biological tissue extract) have provided many opportunities to investigate the changes induced by external stimuli (e.g., drug treatment) or enhance our knowledge of inherent biological variation within subpopulations. This article will focus on the basic principles of metabolic profiling and how the tools (nuclear magnetic resonance [NMR], liquid chromatography-mass spectrometry [LC-MS]) can be applied in toxicology and pathology. Metabolic profiling can complement conventional methodologies and other "omics" technologies in investigating preclinical drug development issues. Case studies will illustrate the value of metabolic profiling in improving our understanding of phospholipidosis and peroxisome proliferation. A key message will be that metabolic profiling offers huge potential to highlight biomarkers and mechanisms in support of toxicology and pathology investigations in preclinical drug development.

UI	MeSH Term	Description	Entries
D008660	Metabolism	The chemical reactions in living organisms by which energy is provided for vital processes and activities and new material is assimilated.	Anabolism,Catabolism,Metabolic Concepts,Metabolic Phenomena,Metabolic Processes,Metabolic Phenomenon,Metabolic Process,Metabolism Concepts,Metabolism Phenomena,Process, Metabolic,Processes, Metabolic,Concept, Metabolic,Concept, Metabolism,Concepts, Metabolic,Concepts, Metabolism,Metabolic Concept,Metabolism Concept,Phenomena, Metabolic,Phenomena, Metabolism,Phenomenon, Metabolic
D010336	Pathology	A specialty concerned with the nature and cause of disease as expressed by changes in cellular or tissue structure and function caused by the disease process.	Pathologies
D004353	Drug Evaluation, Preclinical	Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.	Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D004364	Pharmaceutical Preparations	Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.	Drug,Drugs,Pharmaceutical,Pharmaceutical Preparation,Pharmaceutical Product,Pharmaceutic Preparations,Pharmaceutical Products,Pharmaceuticals,Preparations, Pharmaceutical,Preparation, Pharmaceutical,Preparations, Pharmaceutic,Product, Pharmaceutical,Products, Pharmaceutical
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014116	Toxicology	The science concerned with the detection, chemical composition, and biological action of toxic substances or poisons and the treatment and prevention of toxic manifestations.	Toxinology,Evidence Based Toxicology,Evidence-Based Toxicology,Based Toxicologies, Evidence,Based Toxicology, Evidence,Evidence Based Toxicologies,Evidence-Based Toxicologies,Toxicologies, Evidence Based,Toxicologies, Evidence-Based,Toxicology, Evidence Based,Toxicology, Evidence-Based
D015415	Biomarkers	Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc.	Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D023281	Genomics	The systematic study of the complete DNA sequences (GENOME) of organisms. Included is construction of complete genetic, physical, and transcript maps, and the analysis of this structural genomic information on a global scale such as in GENOME WIDE ASSOCIATION STUDIES.	Functional Genomics,Structural Genomics,Comparative Genomics,Genomics, Comparative,Genomics, Functional,Genomics, Structural