Drug toxicities are not accurately determined from cell culture experiments. Zebrafish embryos are widely-used, versatile toxicity reporters. Both general and specific toxicities in zebrafish correlate very well with toxicities in mice or humans. Problems with fast metabolism of drugs in other animals (i.e. mice) are managed due to passive uptake of drugs from the water providing control over the drug concentration in the animal.
Determination of LD50 (50% lethality dose), MTD (maximally tolerated dose), NOAED (no observed adverse effects dose) and pharmacodynamics in vivo are determined in days.
Specific toxicities to various organs (brain, liver, bone-marrow, kidneys, cardiovascular system, endocrine glands, bone, muscle, GI-tract etc) are determined through the use of transgenic reporter strains.
Jensen LD, Nakamura M, Bräutigam L, Li X, Liu Y, Samani N and Cao Y (2015), ”VEGF-B-neuropilin-1 signaling is spatiotemporally indispensable for vascular and neuronal development in zebrafish”, PNAS, 112(4), pp. E5944-53, Epub.
Bayat N, Lopes VR, Schölermann J, Jensen LD and Cristobal S (2015), “Vascular toxicity of ultra-small TiO2 nanoparticles and signle walled carbon nanotubes in vitro and in vivo”, Biomaterials, Epub
Bräutigam L, Jensen LD, Poschmann G, Nystrom S, Bannenberg S, Dreij K, Lepka K, Prozorovski T, Montano S, Aktas O, Uhlen P, Stühler K, Cao Y, Holmgren A and Berndt C (2013) "Glutaredoxin 2 is essential for oxygen distribution during embryonic development", Proc. Natl. Acad. Sci. U S A. 110(50), pp. 20057-62
Zhang F, Li Y, Kumar A, Tang Z, Lee C, Zhang L, Wang B, Gao Z, Langer HF, Jensen LD, Ma W, Arjunan P, Wong W, Chavakis T, Cao Y and Li X, (2012) “Proliferative and survival effects of PUMA promote angiogenesis”, Cell Reports, 2(5), pp. 1272-85.
Jensen LD, Cao Z, Nakamura M, Yang Y, Bräutigam L, Andersson P, Zhang Y, Wahlberg E, Länne T, Hosaka K and Cao Y, (2012) “Opposing effects of circadian clock genes Bmal1 and Period2 in regulation of VEGF-dependent angiogenesis in developing zebrafish”, Cell Reports, 2(2), pp 231-41.
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