Xenobiotic Metabolomics: Major Impact on the Metabolome

Johnson, Caroline H.; Patterson, Andrew D.; Idle, Jeffrey R.; Gonzalez, Frank J.

doi:10.1146/annurev-pharmtox-010611-134748

Cited by 219 publications

(176 citation statements)

References 88 publications

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“…The metabolome represents all metabolites collection in a biological organism, which are mainly the products of its gene expression. 52 The term metabolomics, is mainly framed for exhaustive, nonbiased, high-throughput analyses of complex metabolite mixtures mainly of plant extracts. Chromatographic fingerprinting technique of various herbal plants has proved to be a comprehensive technique for assessing quality of herbal medicines.…”

Section: Metabolomicsmentioning

confidence: 99%

Omics: A Newer Technique in Herbal Drug Standardization & Quantification

Pandey¹,

Tiwari²,

Shukla³

2016

JYP

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Herbal plants are found abundant in all parts of the world with various uses for its medicinal, pharmaceutical, and nutritional value as well as the ordinary spice in our culinary. Nature is a principal source of herbal medicines. The increasing use of herbal medicine around the globe requires new scientific approaches for their standardization. Evaluation of Physical and chemical parameters are the most common parameters for standardization. Now days, a number of method exists, but not satisfying everyone all over the globe. With the use of newer technique such as omics, (proteomics, metabonomics, transcriptomics etc.), we can easily have depth knowledge of pharmacodyanamics, pharmacokinetics and toxicological characterization of active constituent of an herbal plant. These techniques have made one standard approach for the standardization and modernization of herbal medicine. The modernization of herbal medicine is the need of hour to cater the global demand by means of patient compatibility. The omic technique can also play an important role for the conservation of knowledge of ancient plant species. Moreover omic technique is an important tool for fingerprinting and quality control of herbal medicine. In this review, an emphasis has been made on different techniques of omics and their use in standardization and modernization of herbal plant.

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Section: Metabolomicsmentioning

confidence: 99%

Omics: A Newer Technique in Herbal Drug Standardization & Quantification

Pandey¹,

Tiwari²,

Shukla³

2016

JYP

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“…Another source which determines a person's metabolome is the gut microflora. Environment naturally plays a major role, since diet, exposure to xenobiotics and pollutants alter the metabolites produced [39]. Also people only differing in age and gender also tend to have a different metabolome [39].…”

Section: Factors Affecting Metabolomementioning

confidence: 99%

“…But differences exist between humans and mice in the way which drugs and metabolites are handled. To overcome these differences, genetically modified mouse models were made [39], where, for example, PXR (pregnane X receptor) humanized mice were used to standardize CYP3A experiments [40], PPAR-a humanized mice for studying fibrates and CYP2E1 humanized mice for paracetamol toxicity studies [41]. To overcome differences in gut flora, human microbiome can be set up in a mouse which is germ free at birth.…”

Section: Standardizing Experiments In Metabolomicsmentioning

confidence: 99%

Metabolomics: A Tool Ahead for Understanding Molecular Mechanisms of Drugs and Diseases

2014

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To refer to metabolomics as a new field is injustice to ancient doctors who used ants to diagnose the patients of diabetes having glycosuria. Measuring the levels of molecules in biological fluids believing them to be the representatives of biochemical pathways of carbohydrates, fats, proteins, nucleic acids or xenobiotic metabolism and deciphering meaningful data from it is what can be called as metabolomics, just as high glucose in urine suggests diabetes mellitus. Genomics, epigenetics, proteomics, transcriptomics finally converge to metabolomics, which are the signatures of mechanisms of bodily processes which is why understanding this science can have many applications. Just as a heap of stones does not make a house, having data of metabolite levels does not make it a science. Analyzing this data would help us in constructing biochemical pathways and their interactions. Analyzing the changes caused by a drug in the metabolite levels would help us in deriving the mechanisms by which the drug acts. Comparing metabolite levels in diseased with non-diseased, good-responders with poor-responders to a particular drug can help in identifying new markers of a disease or response to a drug respectively. Also, metabolite levels of an endogenous substrate can tell us the status of a person's metabolizing enzymes and help in drug dose titration. Generating hypothesis by identifying the new molecular markers and testing their utility in clinics seems to be the most promising approach in future. This review narrates the modes of quantifying and identifying metabolome, its proposed applications in diagnosis, monitoring and understanding the diseases and drug responses. We also intend to identify hindrances in using metabolomics in clinical studies or experiments.

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“…Metabolomics is very efficient in identifying novel xenobiotic metabolites and defining the pattern of xenobiotic metabolism, especially when multiple metabolic routes exist in the body (Johnson et al, 2012;Chen et al, 2007a). Besides its value as a tool for probing xenobiotic metabolism, metabolomics is also very capable for examining changes in endogenous metabolism induced by chemical treatment, genetic modification, and health status (Nicholson and Wilson, 2003;Idle and Gonzalez, 2007).…”

Section: Idmentioning

confidence: 99%

Characterization of Differential Cocaine Metabolism in Mouse and Rat through Metabolomics-Guided Metabolite Profiling

et al. 2012

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Rodent animal models have been widely used for studying neurologic and toxicological events associated with cocaine abuse. It is known that the mouse is more susceptible to cocaine-induced hepatotoxicity (CIH) than the rat. However, the causes behind this species-dependent sensitivity to cocaine have not been elucidated. In this study, cocaine metabolism in the mouse and rat was characterized through LC-MS-based metabolomic analysis of urine samples and were further compared through calculating the relative abundance of individual cocaine metabolites. The results showed that the levels of benzoylecgonine, a major cocaine metabolite from ester hydrolysis, were comparable in the urine from the mice and rats treated with the same dose of cocaine. However, the levels of the cocaine metabolites from oxidative metabolism, such as N-hydroxybenzoylnorecgonine and hydroxybenzoylecgonine, differed dramatically between the two species, indicating species-dependent cocaine metabolism. Subsequent structural analysis through accurate mass analysis and LC-MS/ MS fragmentation revealed that N-oxidation reactions, including N-demethylation and N-hydroxylation, are preferred metabolic routes in the mouse, while extensive aryl hydroxylation reactions occur in the rat. Through stable isotope tracing and in vitro enzyme reactions, a mouse-specific a-glucoside of N-hydroxybenzoylnorecgonine and a group of aryl hydroxy glucuronides high in the rat were identified and structurally elucidated. The differences in the in vivo oxidative metabolism of cocaine between the two rodent species were confirmed by the in vitro microsomal incubations. Chemical inhibition of P450 enzymes further revealed that different P450-mediated oxidative reactions in the ecgonine and benzoic acid moieties of cocaine contribute to the species-dependent biotransformation of cocaine.

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Xenobiotic Metabolomics: Major Impact on the Metabolome

Cited by 219 publications

References 88 publications

Omics: A Newer Technique in Herbal Drug Standardization & Quantification

Omics: A Newer Technique in Herbal Drug Standardization & Quantification

Metabolomics: A Tool Ahead for Understanding Molecular Mechanisms of Drugs and Diseases

Characterization of Differential Cocaine Metabolism in Mouse and Rat through Metabolomics-Guided Metabolite Profiling

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