Drug-mediated toxicity: Illuminating the 'bad' in the test tube by means of cellular assays?

Tralau,T.; Luch,A.

doi:10.1016/j.tips.2012.03.015

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Drug-mediated toxicity: Illuminating the 'bad' in the test tube by means of cellular assays?

Health problems are rising worldwide, be it as a consequence of lifestyle and longevity in increasingly affluent societies or due to a sharp rise in bacterial antibiotic resistance. The pharmaceutical industry is caught between high rates of attrition and the rather slow pace of a historically large regulatory system for pharmacological safety. Meanwhile, the past decade has seen a tremendous evolution of the biological toolbox, most notably of cellular assays, stem-cell differentiation and organ-mimicking systems. These systems were readily adapted for lead-compound identification. However, their use as toxicological test systems is lagging behind, not least because of a lack of regulatory acceptance. This review tries to elucidate the scale of the problem and discusses the applicability of the assays currently available, with particular regard to the use of stem cells. -® 2012 Elsevier Ltd. All rights reserved

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Erschienen in:: Trends in pharmacological sciences
Vol. 33, H. 7 (2012), S. 353-364
Band:: 33
Heft:: 7
Datum der Veröffentlichung:: 2012
DOI:: 10.1016/j.tips.2012.03.015
Sprache:: Englisch
Ressourcentyp:: Text
Schlagwörter:: 1 [2 (6 methyl 2 pyridyl)ethyl] 4 (4 methylsulfonylaminobenzoyl)piperidine; 3; 37; acute; adefovir; Adult; AGENT; AGENTS; Analyse; analysis; animal; animal testing; Animals; antibiotic agent; antihistaminic agent; Apoptosis; approach; ASSAY; assessment; atazanavir; Behavior; Berlin; BfR; bioassay; Biological Assay; biological marker; biology; Biomarker; biomarkers; Biomedical Research; bioreactor; blood brain barrier; cancer; CAPACITY; carcinogenesis; carcinogenicity; cardiotoxicity; cardiovascular disease; CELL; cell assay; cell culture; Cell Culture Techniques; Cell Death; Cell Line; cell viability; CELL-LINE; CELLS; Cells,Cultured; CHALLENGE; characterization; chemical; chemical compound; cisapride; clinical; Clinical trial; CLINICAL-TRIALS; COMPOUND; compounds; CULTURE; cyclosporin derivative; CYP2E1; Cytochrome p450; cytotoxicity; DEATH; delayed hypersensitivity; detection; development; developmental toxicity; diclofenac; DIFFERENCE; DIFFERENTIATION; DISCOVERY; DOG; doxorubicin; DRUG; Drug Approval; drug clearance; DRUG DEVELOPMENT; Drug Evaluation,Preclinical; drug excretion; drug metabolism; drug safety; drug screening; drug targeting; DRUG-METABOLISM; ECVAM; Electrophysiology; embryonic stem cell; embryonic stem cells; ENZYME; ENZYMES; evaluation; Extracellular Matrix; FIBROSIS; gene; genome; genomic; genotoxic; genotoxicity; german; Germany; grepafloxacin; growth; growth factor; GROWTH-FACTOR; hazard; HEALTH; Heart; heart arrhythmia; hepatocyte; hepatocytes; hepatotoxicity; high throughput screening; Human; human skin; human skin models; Humans; Hypericum perforatum extract; IDENTIFICATION; immediate type hypersensitivity; immunotoxicity; In Vitro; In vitro system; in vitro test; In vitro tests; in vivo; IN-VITRO; IN-VIVO; INDUCTION; Industry; INHIBITION; inhibitor; innovation; kinetics; lead; line; liver; liver metabolism; liver toxicity; lung toxicity; Mass Spectrometry; MASS-SPECTROMETRY; matrix; MECHANISM; MECHANISMS; metabolism; metabolite; METABOLITES; method; METHODOLOGY; methods; Mice; microarray; minocycline; model; Models; Models,Animal; monitoring; MOUSE; MUSCLE; muscle relaxant agent; natural; nephrotoxicity; neurotoxicity; nifedipine; non-animal; nonhuman; note; OCHRATOXIN; OF-THE-ART; pancreas cell; paracetamol; PATHWAY; PATHWAYS; penicillin derivative; PERSPECTIVE; phage; pharmaceutical; Pharmaceutical Preparations; pharmaceuticals; pharmacology; pluripotent stem cell; potential; POWER; Prediction; prevalidation; priority journal; probe; product; products; PROFILE; PROFILES; protein; proteomic; Proteomics; QT prolongation; QUANTITATION; Rat; REACTIVE METABOLITE; RECOMMENDATIONS; reference; Report; Research; response; review; Risk; Risk Assessment; RISK-ASSESSMENT; rofecoxib; roflumilast; Saccharomyces cerevisiae; Safety; safety assessment; screening; SENSITIVITY; Skin; skin model; sotalol; species; species difference; species differences; SPECTROMETRY; STAGE; standard; STATE; Stem Cells; STRATEGIES; strategy; Stress; studies; study; sunitinib; SYSTEM; SYSTEMS; TARGET; TARGETS; TECHNOLOGIES; TECHNOLOGY; terfenadine; Testing; TESTS; tgn 1412; torsade des pointes; toxic hepatitis; toxicity; toxicity testing; Toxicity Tests; toxicogenomics; toxicology; trends; TRIAL; verapamil; VITRO; VIVO; workshop
DDC-Sachgruppe der DNB:: 570 Biowissenschaften, Biologie
Link URL:: http://www.sciencedirect.com/science/article/pii/S0165614712000557
Einrichtung:: Bundesinstitut für Risikobewertung, Bundesinstitut für Risikobewertung (bis Juni 2014), Abteilung 7 - Produktsicherheit (bis Juni 2014)