Abstract
Since ages, drugs have been used in some form or the other for treatment of several diseases. Safety assessment of drug is an important step required to minimize the drug-associated side effects. Toxicology is an important branch that is required for the safety assessment of drugs. The pharmaceutical companies follow various screening methods during drug development to investigate the toxic effects of effective drugs. The liver, kidney, and heart are the major organs monitored for toxicity evaluation during the drug development. The safety evaluations of drugs are performed at both organ (in vivo) and cellular (in vitro) levels. Considering the increasing demand for alternate to animal models in present times, several cell line-based in vitro models have emerged to assess drug toxicity. Moreover, isolated mitochondria and freshly isolated hepatocytes have also gained importance to understand the mechanism behind the complex processes leading to cellular toxicity. In this chapter, we have discussed the methodologies commonly employed for the safety assessment of drugs.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Alaimo A, Gorojod RM, Kotler ML (2011) The extrinsic and intrinsic apoptotic pathways are involved in manganese toxicity in rat astrocytoma C6 cells. Neurochem Int 59:297–308. https://doi.org/10.1016/j.neuint.2011.06.001
Alchi B, Nishi S, Kondo D et al (2005) Osteopontin expression in acute renal allograft rejection. Kidney Int 67:886–896. https://doi.org/10.1111/j.1523-1755.2005.00153.x
Arvidsson U, Riedl M, Elde R, Meister B (1997) Vesicular acetylcholine transporter (VAChT) protein: A novel and unique marker for cholinergic neurons in the central and peripheral nervous systems. J Comp Neurol 378:454–467. https://doi.org/10.1002/(SICI)1096-9861(19970224)378:4<454::AID-CNE2>3.0.CO;2-1
Astashkina A, Mann B, Grainger DW (2012) A critical evaluation of in-vitro cell culture models for high-throughput drug screening and toxicity. Pharmacol Ther 134:82–106. https://doi.org/10.1016/j.pharmthera.2012.01.001
Babot Z, Vilaró MT, Suñol C (2007) Long-term exposure to dieldrin reduces γ-aminobutyric acid type A and N-methyl-D-aspartate receptor function in primary cultures of mouse cerebellar granule cells. J Neurosci Res 85:3687–3695
Bader A, Rinkes IH, Closs EI et al (1992) A stable long-term hepatocyte culture system for studies of physiologic processes: cytokine stimulation of the acute phase response in rat and human hepatocytes. Biotechnol Prog 8:219–225
Bailly V, Zhang Z, Meier W et al (2002) Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration. J Biol Chem 277:39739–39748. https://doi.org/10.1074/jbc.M200562200
Bajaj P, Chowdhury SK, Yucha R et al (2018) Emerging kidney models to investigate metabolism, transport, and toxicity of drugs and xenobiotics. Drug Metab Dispos 46:1692–1702. https://doi.org/10.1124/dmd.118.082958
Bajpai P, Sangar MC, Singh S et al (2013) Metabolism of 1-methyl-4-phenyl-1,2,3/6-tetrahydropyridine by mitochondrion-targeted cytochrome P450 2D6 implications in parkinson disease. J Biol Chem 288:4436–4451. https://doi.org/10.1074/jbc.M112.402123
Banker GGK (1998) Culturing nerve cells, 2nd edn. MIT, Cambridge, MA, pp 11–36
Barbosa DJ, Capela JP, Silva R et al (2014a) The mixture of “ecstasy” and its metabolites is toxic to human SH-SY5Y differentiated cells at in-vivo relevant concentrations. Arch Toxicol 88:455–473. https://doi.org/10.1007/s00204-013-1120-7
Barbosa DJ, Capela JP, Silva R et al (2014b) Ecstasy-induced toxicity in SH-SY5Y differentiated cells: Role of hyperthermia and metabolites. Arch Toxicol 88:515–531. https://doi.org/10.1007/s00204-013-1147-9
Baron S, Tyring SK, Fleischmann WR, Coppenhaver DH, Niesel DW, Klimpel GR, Stanton GJHT (1991) The interferons: mechanisms of action and clinical applications. Jama 266:1375–1383
Bayir H, Marion DW, Puccio AM et al (2004) Marked gender effect on lipid peroxidation after severe traumatic brain injury in adult patients. J Neurotrauma 21:1–8. https://doi.org/10.1089/089771504772695896
Belogurov AA, Kurkova IN, Friboulet A et al (2008) Recognition and degradation of myelin basic protein peptides by serum autoantibodies: novel biomarker for multiple sclerosis. J Immunol 180:1258–1267. https://doi.org/10.4049/jimmunol.180.2.1258
Benda P, Lightbody J, Sato G, Levine LSW (1968) Differentiated rat glial cell strain in tissue culture. Science (80- ) 161:370–371. https://doi.org/10.1126/science.161.3839.371
Berger RP, Adelson PD, Richichi R, Kochanek PM (2006) Serum biomarkers after traumatic and hypoxemic brain injuries: insight into the biochemical response of the pediatric brain to inflicted brain injury. Dev Neurosci 28:327–335. https://doi.org/10.1159/000094158
Berger RP, Hayes RL, Richichi R et al (2012) Serum concentrations of ubiquitin C-terminal hydrolase-l1 and αiI-spectrin breakdown product 145kDa correlate with outcome after pediatric TBI. J Neurotrauma 29:162–167. https://doi.org/10.1089/neu.2011.1989
Bernard AM, Vyskocil AA, Mahieu P, Lauwerys RR (1987) Assessment of urinary retinol-binding protein as an index of proximal tubular injury. Clin Chem 33:775–779. https://doi.org/10.1093/clinchem/33.6.775
Berntsen HF, Wigestrand MB, Bogen IL et al (2013) Mechanisms of penitrem-induced cerebellar granule neuron death in-vitro: Possible involvement of GABAA receptors and oxidative processes. Neurotoxicology 35:129–136. https://doi.org/10.1016/j.neuro.2013.01.004
Bi YA, Kazolias D, Duignan DB (2006) Use of cryopreserved human hepatocytes in sandwich culture to measure hepatobiliary transport. Drug Metab Dispos 34:1658–1665. https://doi.org/10.1124/dmd.105.009118
Biagini CP, Boissel E, Borde F et al (2006) Investigation of the hepatotoxicity profile of chemical entities using Liverbeads® and WIF-B9 in-vitro models. Toxicol Vitr 20:1051–1059. https://doi.org/10.1016/j.tiv.2006.01.013
Biedler JL, Schachner M (1978) Multiple neurotransmitter synthesis by human neuroblastoma cell lines and clones. Cancer Res 38:3751–3757
Birnbaum LS, Stokes WS (2010) Safety testing: moving toward alternative methods. Environ Health Perspect 118:12–13. https://doi.org/10.1289/ehp.0901704
Boelsterli UA (2003) Diclofenac-induced liver injury: a paradigm of idiosyncratic drug toxicity. Toxicol Appl Pharmacol 192:307–322. https://doi.org/10.1016/S0041-008X(03)00368-5
Boess F, Kamber M, Romer S et al (2003) Gene expression in two hepatic cell lines, cultured primary hepatocytes, and liver slices compared to the in-vivo liver gene expression in rats: possible implications for toxicogenomics use of in-vitro systems. Toxicol Sci 73:386–402. https://doi.org/10.1093/toxsci/kfg064
Bögler O (1997) Isolation and purification of primary oligodendrocyte precursors. Curr Protoc Neurosci 00:1–9. https://doi.org/10.1002/0471142301.ns0304s00
Bonventre JV, Vaidya VS, Schmouder R, Feig PDF (2010) Next-generation biomarkers for detecting kidney toxicity. Nat Biotechnol 28:436–440. https://doi.org/10.1038/nbt0510-436.Next-generation
Boo D, Knight A (2009) Replacing, reducing and refining procedures in animal research. J Oral Tissue Eng 6:215–222. https://doi.org/10.11223/jarde.6.215
Borregaard N, Sehested M, Nielsen BS et al (1995) Biosynthesis of granule proteins in normal human bone marrow cells. Gelatinase is a marker of terminal neutrophil differentiation. Blood 85:812–817. https://doi.org/10.1182/blood.v85.3.812.bloodjournal853812
Bort R, Ponsoda X, Jover R, Gómez-Lechón MJCJ (1998) Diclofenac toxicity to hepatocytes: a role for drug metabolism in cell toxicity. J Pharmacol Exp Ther 288:65–72
Borzelleca JF (2000) Paracelsus: Herald of modern toxicology. Toxicol Sci 53:2–4. https://doi.org/10.1093/toxsci/53.1.2
Braiterman LT, Hubbard AL (2009) The liver. John Wiley & Sons, Ltd
Brophy GM, Mondello S, Papa L et al (2011) Biokinetic analysis of ubiquitin C-terminal hydrolase-L1 (UCH-L1) in severe traumatic brain injury patient biofluids. J Neurotrauma 28:861–870. https://doi.org/10.1089/neu.2010.1564
Burke AS, MacMillan-Crow LA, Hinson JA (2010) The hepatocyte suspension assay is superior to the cultured hepatocyte assay for determining mechanisms of acetaminophen hepatotoxicity relevant to in-vivo toxicity. Chem Res Toxicol 23:1855–1858. https://doi.org/10.1021/tx1003744
Capela JP, da Costa AS, Costa VM et al (2013) The neurotoxicity of hallucinogenic amphetamines in primary cultures of hippocampal neurons. Neurotoxicology 34:254–263. https://doi.org/10.1016/j.neuro.2012.09.005
Capela JP, Macedo C, Branco PS et al (2007) Neurotoxicity mechanisms of thioether ecstasy metabolites. Neuroscience 146:1743–1757. https://doi.org/10.1016/j.neuroscience.2007.03.028
Chang SY, Weber EJ, Ness KV, Eaton DLKE (2016) Liver and kidney on chips: microphysiological models to understand transporter function. Clin Pharmacol Ther 100:464–478. https://doi.org/10.1002/cpt.436.Liver
Chang SY, Weber EJ, Sidorenko VS et al (2017) Human liver-kidney model elucidates the mechanisms of aristolochic acid nephrotoxicity. JCI Insight 2:1–14. https://doi.org/10.1172/jci.insight.95978
Chen JX, Sun YJ, Wang P et al (2013) Induction of autophagy by TOCP in differentiated human neuroblastoma cells lead to degradation of cytoskeletal components and inhibition of neurite outgrowth. Toxicology 310:92–97. https://doi.org/10.1016/j.tox.2013.05.012
Chen M, Suzuki A, Borlak J et al (2015) Drug-induced liver injury: interactions between drug properties and host factors. J Hepatol 63:503–514. https://doi.org/10.1016/j.jhep.2015.04.016
Choudhury D, Ahmed Z (2006) Drug-associated renal dysfunction and injury. Nat Clin Pract Nephrol 2:80–91. https://doi.org/10.1038/ncpneph0076
Ciccarone V, Spengler BA, Meyers MB et al (1989) Phenotypic diversification in human neuroblastoma cells: expression of distinct neural crest lineages. Cancer Res 49:219–225
Cook D, Brown D, Alexander R et al (2014) Lessons learned from the fate of AstraZeneca’s drug pipeline: A five-dimensional framework. Nat Rev Drug Discov 13:419–431. https://doi.org/10.1038/nrd4309
Council N.R. (2012) The future of animals, cells, models, and systems in research, development, education, and testing; Proceedings of a symposium. In: National Academy of Sciences. Washington DC, USA
Cunha-Oliveira T, Rego AC, Cardoso SM et al (2006) Mitochondrial dysfunction and caspase activation in rat cortical neurons treated with cocaine or amphetamine. Brain Res 1089:44–54. https://doi.org/10.1016/j.brainres.2006.03.061
Das S (2018) Extrapolation of In-vitro results to predict human toxicity. Academic Press
De Vries GH, Boullerne AI (2010) Glial cell lines: an overview. Neurochem Res 35:1978–2000. https://doi.org/10.1007/s11064-010-0318-9
DelRaso NJ (1993) In-vitro methodologies for enhanced toxicity testing. Toxicol Lett 68:91–99
DesRochers TM, Suter L, Roth A, Kaplan DL (2013) Bioengineered 3D human kidney tissue, a platform for the determination of nephrotoxicity. PLoS One 8. https://doi.org/10.1371/journal.pone.0059219
DiMasi JA, Hansen RW, Grabowski HG (2003) The price of innovation: new estimates of drug development costs. J Health Econ 22:151–185. https://doi.org/10.1016/S0167-6296(02)00126-1
Donovan KL, Coles GA, Williams JD (1994) An ELISA for the detection of type IV collagen in human urine—application to patients with glomerulonephritis. Kidney Int 46:1431–1437. https://doi.org/10.1038/ki.1994.415
Dorato MA, Buckley LA (2007) Toxicology testing in drug discovery and development. Curr Protoc Toxicol Chapter 19:1–35. https://doi.org/10.1002/0471141755.tx1901s31
Duval DL, Sieg DJBR (1995) Regulation of hepatic nitric oxide synthase by reactive oxygen intermediates and glutathione. Arch Biochem Biophys 316:699–706
Eaton MJ, Duplan H (2004) Useful cell lines derived from the adrenal medulla. Mol Cell Endocrinol 228:39–52. https://doi.org/10.1016/j.mce.2003.02.001
Eisenhofer G, Klink B, Richter S et al (2017) Metabologenomics of phaeochromocytoma and paraganglioma: an integrated approach for personalised biochemical and genetic testing. Clin Biochem Rev 38:69–100
Ekins S, Murray GI, Burke MD, Williams JA, Marchant NCHG (1995) Quantitative differences in phase I and II metabolism between rat precision-cut liver slices and isolated hepatocytes. Drug Metab Dispos 23:1274–1279
Emeigh Hart SG (2005) Assessment of renal injury in-vivo. J Pharmacol Toxicol Methods 52:30–45. https://doi.org/10.1016/j.vascn.2005.04.006
Esmaeilzadeh E, Gardaneh M, Gharib E, Sabouni F (2013) Shikonin protects dopaminergic cell line PC12 against 6-hydroxydopamine-mediated neurotoxicity via both glutathione-dependent and independent pathways and by inhibiting apoptosis. Neurochem Res 38:1590–1604. https://doi.org/10.1007/s11064-013-1061-9
Falnoga I, Šlejkovec Z, Pucer A et al (2007) Arsenic metabolism in multiple myeloma and astrocytoma cells. Biol Trace Elem Res 116:5–28. https://doi.org/10.1007/BF02685915
Fang H, Harris SC, Liu Z et al (2016) FDA drug labeling: rich resources to facilitate precision medicine, drug safety, and regulatory science. Drug Discov Today 21:1566–1570. https://doi.org/10.1016/j.drudis.2016.06.006
Faria J, Ahmed S, Gerritsen KGF et al (2019) Kidney-based in-vitro models for drug-induced toxicity testing. Arch Toxicol 93:3397–3418. https://doi.org/10.1007/s00204-019-02598-0
Fath T, Ke YD, Gunning P et al (2009) Primary support cultures of hippocampal and substantia nigra neurons. Nat Protoc 4:78–85. https://doi.org/10.1038/nprot.2008.199
Fedecostante M, Onciu OG, Westphal KGC, Masereeuw R (2017) Towards a bioengineered kidney: recellularization strategies for decellularized native kidney scaffolds. 40:150–158. https://doi.org/10.5301/ijao.5000564
Ferguson MA, Vaidya VS, Bonventre J (2008) Biomarkers of nephrotoxic acute kidney injury. Toxicology 245:182–193. https://doi.org/10.1016/j.tox.2007.12.024.Biomarkers
Ferreira PS, Nogueira TB, Costa VM et al (2013) Neurotoxicity of “ecstasy” and its metabolites in human dopaminergic differentiated SH-SY5Y cells. Toxicol Lett 216:159–170. https://doi.org/10.1016/j.toxlet.2012.11.015
Finn WF, Porter G (2003) Urinary biomarkers and nephrotoxicity. Springer, Dordrecht
Fisher RL, Shaughnessy RP, Jenkins PM et al (1995) Dynamic organ culture is superior to multiwell plate culture for maintaining precision-cut tissue slices: optimization of tissue slice culture, part 1. Toxicol Mech Methods 5:99–113. https://doi.org/10.3109/15376519509045905
Gad SC (1996) ICLAS proceedings: preclinical toxicity testing in the development of new therapeutic agents. Scand J Lab Anim Sci. Supplement (Denmark)
Gad SC (2009) Drug safety evaluation, 2nd edn. John Wiley & Sons, Inc, Hoboken, NJ
Gad SC (2015) Animal models in toxicology, 3rd edn. Marcel Dekker, Marcel Dekker, New York
Gad SC (2017) The application of in-vitro techniques in drug safety assessment. Drug Saf Eval 553–582. https://doi.org/10.1002/9781119097440.ch27
Ghantous HN, Fernando J, Gandolfi AJ, Brendel K (1992) Sevoflurane is biotransformed by guinea pig liver slices but causes minimal cytotoxicity. Anesth Analg 75:436–440. https://doi.org/10.1213/00000539-199209000-00021
Giezen TJ, Mantel-Teeuwisse AK, Straus SMJM et al (2008) Safety-related regulatory actions for biologicals approved in the United States and the European Union. JAMA – J Am Med Assoc 300:1887–1896. https://doi.org/10.1001/jama.300.16.1887
Giordano G, Kavanagh TJ, Costa L (2009) Mouse cerebellar astrocytes protect cerebellar granule neurons against toxicity of the polybrominated diphenyl ether (PBDE) mixture DE-71. Neurotoxicology 30:326–329. https://doi.org/10.1016/j.neuro.2008.12.009.Mouse
Gokhale BTMS, Zurlo JYJ (1997) Cytochrome P-450 1A1/1A2 induction, albumin secretion, and histological changes in cultured rat liver slices. In-vitro Toxicol 8:357–368
Gómez-Lechón MJ, Castell JV, Donato MT (2008) An update on metabolism studies using human hepatocytes in primary culture. Expert Opin Drug Metab Toxicol 4:837–854. https://doi.org/10.1517/17425255.4.7.837
Gómez-Lechón MJ, Donato LA, López PTMA, JV C (1988) Liver cells and drugs. Colloque INSERM/John Libbey Ltd.
Gomez-Lechon MJ, Lahoz A, Gombau L et al (2010) In-vitro evaluation of potential hepatotoxicity induced by drugs. Curr Pharm Des 16:1963–1977. https://doi.org/10.2174/138161210791208910
Gradinaru D, Minn AL, Artur Y et al (2012) Effect of oxidative stress on UDP-glucuronosyltransferases in rat astrocytes. Toxicol Lett 213:316–324. https://doi.org/10.1016/j.toxlet.2012.07.014
Griffin SJ, Houston JB (2005) Prediction of in-vitro intrinsic clearance from hepatocytes: comparison of suspensions and monolayer cultures. Drug Metab Dispos 33:115–120. https://doi.org/10.1124/dmd.33.1.115
Guder WG, Hofmann W (1992) Markers for the diagnosis and monitoring of renal tubular lesions. Clin Nephrol 38:S3–7
Guguen-Guillouzo CGA (2010) General review on in-vitro hepatocyte models and their applications. Hepatocytes 640:1–40
Guillouzo A (1998) Liver cell models in in-vitro toxicology. Environ Health Perspect 106:511–532. https://doi.org/10.1289/ehp.98106511
Guillouzo A, Morel F, Langouët S et al (1997) Use of hepatocyte cultures for the study of hepatotoxic compounds. J Hepatol Suppl 26:73–80. https://doi.org/10.1016/s0168-8278(97)80499-0
Guo D, Liu J, Wang W et al (2013) Alteration in abundance and compartmentalization of inflammation-related miRNAs in plasma after intracerebral hemorrhage. Stroke 44:1739–1742. https://doi.org/10.1161/STROKEAHA.111.000835
Hashemi E, Till CIC (1999) Stability of Phase II conjugation systems in cultured precision-cut rat hepatic slices. Toxicol Vitr 13:459–466
Hashimoto M, Hibi M (2012) Development and evolution of cerebellar neural circuits. Dev Growth Differ 54:373–389. https://doi.org/10.1111/j.1440-169X.2012.01348.x
He K, Talaat RE, Pool WF et al (2004) Metabolic activation of troglitazone: identification of a reactive metabolite and mechanisms involved. Drug Metab Dispos 32:639–646. https://doi.org/10.1124/dmd.32.6.639
Herget-Rosenthal S, Poppen D, Hüsing J et al (2004) Prognostic value of tubular proteinuria and enzymuria in nonoliguric acute tubular necrosis. Clin Chem 50:552–558. https://doi.org/10.1373/clinchem.2003.027763
Hettiarachchi NT, Boyle JP, Bauer CC, Dallas ML, Pearson HA, Hara S, Gamper NPC (2012) Peroxynitrite mediates disruption of Ca2+ homeostasis by carbon monoxide via Ca2+ ATPase degradation. Antioxid Redox Signal 17:744–755
Hewitt NJ, Lechón MJG, Houston JB et al (2007) Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies. Drug Metab Rev 39:159–234. https://doi.org/10.1080/03602530601093489
Hogberg HT, Kinsner-Ovaskainen A, Coecke S et al (2009) mRNA expression is a relevant tool to identify developmental neurotoxicants using an in-vitro approach. Toxicol Sci 113:95–115. https://doi.org/10.1093/toxsci/kfp175
Horii Y, Iwano M, Hirata E, Shiiki H, Fujii Y, Dohi K IH (1993) Role of interleukin-6 in the progression of mesangial proliferative glomerulonephritis. In: Kidney International Supplement. p 39
Im AR, Kim YH, Uddin MR et al (2013) Betaine protects against rotenone-induced neurotoxicity in PC12 cells. Cell Mol Neurobiol 33:625–635. https://doi.org/10.1007/s10571-013-9921-z
Jansen J, De Napoli IE, Fedecostante M et al (2015) Human proximal tubule epithelial cells cultured on hollow fibers: living membranes that actively transport organic cations. Sci Rep 5:1–12. https://doi.org/10.1038/srep16702
Jansen J, Fedecostante M, Wilmer MJ et al (2016) Bioengineered kidney tubules efficiently excrete uremic toxins. Sci Rep 6:1–12. https://doi.org/10.1038/srep26715
Jansen J, Schophuizen CMS, Wilmer MJ et al (2014) A morphological and functional comparison of proximal tubule cell lines established from human urine and kidney tissue. Exp Cell Res 323:87–99. https://doi.org/10.1016/j.yexcr.2014.02.011
Jauregui HO, McMillan PN, Hevey KNS (2016) A quantitative analysis of lectin binding to adult rat hepatocyte cell surfaces. Cell Vitr 24:401–412
Jenkinson SE, Chung GW, van Loon E et al (2012) The limitations of renal epithelial cell line HK-2 as a model of drug transporter expression and function in the proximal tubule. Pflugers Arch 464:601–611. https://doi.org/10.1007/s00424-012-1163-2
Jiménez A, Jordà EG, Verdaguer E et al (2004) Neurotoxicity of amphetamine derivatives is mediated by caspase pathway activation in rat cerebellar granule cells. Toxicol Appl Pharmacol 196:223–234. https://doi.org/10.1016/j.taap.2003.12.017
Jordt SE, Bautista DM, Chuang HH et al (2004) Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427:260–265. https://doi.org/10.1038/nature02282
Jung JE, Moon JY, Ghil SH, Yoo BS (2009) 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibits neurite outgrowth in differentiating human SH-SY5Y neuroblastoma cells. Toxicol Lett 188:153–156. https://doi.org/10.1016/j.toxlet.2009.04.004
Kaur P, Evje L, Aschner M, Syversen T (2010) The in-vitro effects of Trolox on methylmercury-induced neurotoxicity. Toxicology 276:73–78. https://doi.org/10.1016/j.tox.2010.07.006
Kharasch ED, Schroeder JL, Bammler T et al (2006) Gene expression profiling of nephrotoxicity from the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl Ether (“Compound A”) in Rats. Toxicol Sci 90:419–431. https://doi.org/10.1093/toxsci/kfj088
Kilpatrick DL, Wang W, Gronostajski RLE (2012) Nuclear factor I and cerebellar granule neuron development: an intrinsic–extrinsic interplay. Cerebellum 11:41–49. https://doi.org/10.1007/s12311-010-0227-0.Nuclear
Koh W, Pan W, Gawad C, Fan HC, Kerchner GA, Wyss-Coray T, Blumenfeld YJ, El-Sayed YYQS (2014) Noninvasive in-vivo monitoring of tissue-specific global gene expression in humans. Proc Natl Acad Sci U S A 111:7361–7366. https://doi.org/10.1073/pnas.1411381111
Kreisl WC, Jenko KJ, Hines CS et al (2013) A genetic polymorphism for translocator protein 18 kDa affects both in-vitro and in-vivo radioligand binding in human brain to this putative biomarker of neuroinflammation. J Cereb Blood Flow Metab 33:53–58. https://doi.org/10.1038/jcbfm.2012.131
Kumaria A, Tolias CM (2008) In-vitro models of neurotrauma. Br J Neurosurg 22:200–206. https://doi.org/10.1080/02688690701772413
Kyeong IG, Eum WS, Choi SY, Kang JH (2013) Oxidative modification of neurofilament-L and neuronal cell death induced by the catechol neurotoxin, tetrahydropapaveroline. Toxicol Lett 217:59–66. https://doi.org/10.1016/j.toxlet.2012.11.029
Lambert JDC, Jones RSG, Andreasen M et al (1989) The role of excitatory amino acids in synaptic transmission in the hippocampus. Comp Biochem Physiol -- Part A Physiol 93:195–201. https://doi.org/10.1016/0300-9629(89)90207-7
Lawson SN, Biscoe TJ (1979) Development of mouse dorsal root ganglia: an autoradiographic and quantitative study. J Neurocytol 8:265–274. https://doi.org/10.1007/BF01236122
LeCluyse EL (2001) Human hepatocyte culture systems for the in-vitro evaluation of cytochrome P450 expression and regulation. Eur J Pharm Sci 13:343–368. https://doi.org/10.1016/S0928-0987(01)00135-X
LeCluyse EL, Bullock PL, Parkinson A (1996) Strategies for restoration and maintenance of normal hepatic structure and function in long-term cultures of rat hepatocytes. Adv Drug Deliv Rev 22:133–186. https://doi.org/10.1016/S0169-409X(96)00418-8
Leeman WR, van de Gevel IA, Rutten AAJJL (1995) Cytotoxicity of retinoic acid, menadione and aflatoxin B1 in rat liver slices using Netwell inserts as a new culture system. Toxicol Vitr 9. https://doi.org/10.1016/0887-2333(95)00008-V
Lerche-Langrand C, Toutain HJ (2000) Precision-cut liver slices: characteristics and use for in-vitro pharmaco-toxicology. Toxicology 153:221–253. https://doi.org/10.1016/S0300-483X(00)00316-4
Lewis SB, Wolper R, Chi YY et al (2010) Identification and preliminary characterization of ubiquitin C terminal hydrolase 1 (UCHL1) as a biomarker of neuronal loss in aneurysmal subarachnoid hemorrhage. J Neurosci Res 88:1475–1484. https://doi.org/10.1002/jnr.22323
Li AP (2004) Accurate prediction of human drug toxicity: a major challenge in drug development. Chem Biol Interact 150:3–7. https://doi.org/10.1016/j.cbi.2004.09.008
Li JY, Matias J, Scudiero DA, Hite KM et al (2001) P450 enzyme expression patterns in the NCI human tumor cell line panel. Drug Metab Dispos 29:304–312
Lijinsky W (1988) Importance of animal experiments in carcinogenesis research. Environ Mol Mutagen 11:307–314
Liu X, Piao F, Li Y (2013) Protective effect of taurine on the decreased biogenic amine neurotransmitter levels in the brain of mice exposed to arsenic. InTaurine 776:277–287
López-Doménech G, Serrat R, Mirra S et al (2012) The Eutherian Armcx genes regulate mitochondrial trafficking in neurons and interact with Miro and Trak2. Nat Commun 3. https://doi.org/10.1038/ncomms1829
Lübberstedt M, Müller-Vieira U, Mayer M et al (2011) HepaRG human hepatic cell line utility as a surrogate for primary human hepatocytes in drug metabolism assessment in-vitro. J Pharmacol Toxicol Methods 63:59–68. https://doi.org/10.1016/j.vascn.2010.04.013
MacDonald C, Vass M, Willett B, Scott AGH (1994) Expression of liver functions in immortalised rat hepatocyte cell lines. Hum Exp Toxicol 13:439–444
Maekawa F, Tsuboi T, Oya M et al (2013) Effects of sodium arsenite on neurite outgrowth and glutamate AMPA receptor expression in mouse cortical neurons. Neurotoxicology 37:197–206. https://doi.org/10.1016/j.neuro.2013.05.006
Malin SA, Davis BM, Molliver DC (2007) Production of dissociated sensory neuron cultures and considerations for their use in studying neuronal function and plasticity. Nat Protoc 2:152–160. https://doi.org/10.1038/nprot.2006.461
Martins JB, Bastos MDL, Carvalho F, Capela JP (2013) Differential effects of methyl-4-phenylpyridinium ion, rotenone, and Paraquat on differentiated SH-SY5Y cells. J Toxicol 2013. https://doi.org/10.1155/2013/347312
May JE, Xu J, Morse HR et al (2009) Toxicity testing: the search for an in-vitro alternative to animal testing. Br J Biomed Sci 66:160–165. https://doi.org/10.1080/09674845.2009.11730265
McCarter GC, Reichling DB, Levine JD (1999) Mechanical transduction by rat dorsal root ganglion neurons in-vitro. Neurosci Lett 273:179–182. https://doi.org/10.1016/S0304-3940(99)00665-5
McDonald MG, Rettie AE (2007) Sequential metabolism and bioactivation of the hepatotoxin benzbromarone: formation of glutathione adducts from a catechol intermediate. Chem Res Toxicol 20:1833–1842. https://doi.org/10.1021/tx7001228
Meacham CA, Freudenrich TM, Anderson WL et al (2005) Accumulation of methylmercury or polychlorinated biphenyls in in-vitro models of rat neuronal tissue. Toxicol Appl Pharmacol 205:177–187. https://doi.org/10.1016/j.taap.2004.08.024
Milne GL, Morrow JD (2006) Isoprostanes and related compounds: update 2006. Antioxidants Redox Signal 8:1379–1384. https://doi.org/10.1089/ars.2006.8.1379
Misko A, Jiang S, Wegorzewska I et al (2010) Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. J Neurosci 30:4232–4240. https://doi.org/10.1523/JNEUROSCI.6248-09.2010
Mogensen CE (1971) Urinary albumin excretion in early and long-term juvenile diabetes. Scand J Clin Lab Invest 28:183–193. https://doi.org/10.3109/00365517109086899
Molyneaux BJ, Arlotta P, Menezes JRL, Macklis JD (2007) Neuronal subtype specification in the cerebral cortex. Nat Rev Neurosci 8:427–437. https://doi.org/10.1038/nrn2151
Mondello S, Gabrielli A, Catani S et al (2012) Increased levels of serum MAP-2 at 6-months correlate with improved outcome in survivors of severe traumatic brain injury. Brain Inj 26:1629–1635. https://doi.org/10.3109/02699052.2012.700083
Nelson KF, Acosta D, Bruckner JV (1982) Long-term maintenance and induction of cytochrome P-450 in primary cultures of rat hepatocytes. Biochem Pharmacol 31:2211–2214. https://doi.org/10.1016/0006-2952(82)90521-4
Nerlich AG, Schleicher ED, Wiest I et al (1994) Immunohistochemical localization of collagen VI in diabetic glomeruli. Kidney Int 45:1648–1656. https://doi.org/10.1038/ki.1994.216
Nieskens TTG, Peters JGP, Schreurs MJ et al (2016) A human renal proximal tubule cell line with stable organic anion transporter 1 and 3 expression predictive for antiviral-induced toxicity. AAPS J 18:465–475. https://doi.org/10.1208/s12248-016-9871-8
Noé J, Portmann R, Brun ME, Funk C (2007) Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP) substrates on OATP1B1, OATP2B1, and OATP1B3. Drug Metab Dispos 35:1308–1314. https://doi.org/10.1124/dmd.106.012930
Nomura S, Wills AJ, Edwards DR et al (1988) Developmental expression of 2ar (osteopontin) and SPARC (Osteonectin) RNA as revealed by in situ hybridization. J Cell Biol 106:441–450. https://doi.org/10.1083/jcb.106.2.441
O’Brien P, Siraki A (2005) Accelerated cytotoxicity mechanism screening using drug metabolising enzyme modulators. Curr Drug Metab 6:101–109. https://doi.org/10.2174/1389200053586082
O’Brien PJ, Irwin W, Diaz D et al (2006) High concordance of drug-induced human hepatotoxicity with in-vitro cytotoxicity measured in a novel cell-based model using high content screening. Arch Toxicol 80:580–604. https://doi.org/10.1007/s00204-006-0091-3
O’Callaghan JP, Sriram K (2005) Glial fibrillary acidic protein and related glial proteins as biomarkers of neurotoxicity. Expert Opin Drug Saf 4:433–442. https://doi.org/10.1517/14740338.4.3.433
Ohlsson S, Wieslander J, Segelmark M (2003) Increased circulating levels of proteinase 3 in patients with anti-neutrophilic cytoplasmic autoantibodies-associated systemic vasculitis in remission. Clin Exp Immunol 131:528–535. https://doi.org/10.1046/j.1365-2249.2003.02083.x
Oldberg A, Franzen A, Heinegard D (1986) Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. Proc Natl Acad Sci U S A 83:8819–8823. https://doi.org/10.1073/pnas.83.23.8819
Oliveira JMA, Chen S, Almeida S et al (2006) Mitochondrial-dependent Ca2+ handling in Huntington’s disease striatal cells: effect of histone deacetylase inhibitors. J Neurosci 26:11174–11186. https://doi.org/10.1523/JNEUROSCI.3004-06.2006
Påhlman S, Ruusala AI, Abrahamsson L et al (1983) Kinetics and concentration effects of TPA-induced differentiation of cultured human neuroblastoma cells. Cell Differ 12:165–170. https://doi.org/10.1016/0045-6039(83)90006-4
Park BK, Kitteringham NR, Maggs JL et al (2005) The role of metabolic activation in drug-induced hepatotoxicity. Annu Rev Pharmacol Toxicol 45:177–202. https://doi.org/10.1146/annurev.pharmtox.45.120403.100058
Patarca R, Freeman GJ, Singh RP et al (1989) Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene. Definition of a novel T cell-dependent response associated with genetic resistance to bacterial infection. J Exp Med 170:145–161. https://doi.org/10.1084/jem.170.1.145
Pearce RE, Uetrecht JP, Leeder JS (2005) Pathways of carbamazepine bioactivation in-vitro: II. The role of human cytochrome P450 enzymes in the formation of 2-hydroxyiminostilbene. Drug Metab Dispos 33:1819–1826. https://doi.org/10.1124/dmd.105.004861
Pfragner R, Behmel A, Smith DP et al (1998) First continuous human pheochromocytoma cell line: KNA biological, cytogenetic and molecular characterization of KNA cells. J Neurocytol 27:175–186. https://doi.org/10.1023/A:1006959625068
Philbert MA, Beiswanger CM, Manson MM, Green, Novak RF, Primiano T, Reuhl KRLH (1995) Glutathione S-transferases and gamma-glutamyl transpeptidase in the rat nervous systems: a basis for differential susceptibility to neurotoxicants. Neurotoxicology 16:349–362
Pichler WJ (2002) Pharmacological interaction of drugs with antigen-specific immune receptors: the pi concept. Curr Opin Allergy Clin Immunol 2:301–305
Podratz JL, Knight AM, Ta LE et al (2011) Cisplatin induced Mitochondrial DNA damage in dorsal root ganglion neurons. Neurobiol Dis 41:661–668. https://doi.org/10.1016/j.nbd.2010.11.017
Popp RL, Reneau JC, Dertien J (2008) Cerebellar granule cells cultured from adolescent rats express functional NMDA receptors: an in-vitro model for studying the developing cerebellum. J Neurochem 106:900–911
Presgraves SP, Ahmed T, Borwege S, Joyce JN (2003) Terminally differentiated SH-SY5Y cells provide a model system for studying neuroprotective effects of dopamine agonists. Neurotox Res 5:579–598. https://doi.org/10.1007/BF03033178
Prinsen BHCMT, Sain-van D, der Velden MGM, Kaysen GA et al (2001) Transferrin synthesis is increased in nephrotic patients insufficiently to replace urinary losses. J Am Soc Nephrol 12:1017–1025. https://doi.org/10.1681/asn.v1251017
Pritt ML, Hall DG, Jordan WH et al (2014) Initial biological qualification of SBDP-145 as a biomarker of compound-induced neurodegeneration in the rat. Toxicol Sci 141:398–408. https://doi.org/10.1093/toxsci/kfu136
Qiu B, Sun X, Zhang D et al (2012) TRAIL and paclitaxel synergize to kill U87 cells and U87-derived stem-like cells in-vitro. Int J Mol Sci 13:9142–9156. https://doi.org/10.3390/ijms13079142
Reid GFM (2001) Cold current in thermoreceptive neurons. Nature 413:480
Roberts RA, Kavanagh SL, Mellor HR, Pollard CE, Robinson SPS (2014) Reducing attrition in drug development: smart loading preclinical safety assessment. Drug Discov Today 19:341–347
Roberts RA, Smith RA, Safe S et al (2010) Toxicological and pathophysiological roles of reactive oxygen and nitrogen species. Toxicology 276:85–94. https://doi.org/10.1016/j.tox.2010.07.009
Rohacova J, Marin ML, Martínez-Romero A et al (2008) Photophysical characterization and flow cytometry applications of cholylamidofluorescein, a fluorescent bile acid scaffold. Photochem Photobiol Sci 7:860–866. https://doi.org/10.1039/b806366d
Rupprecht R, Papadopoulos V, Rammes G et al (2010) Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat Rev Drug Discov 9:971–988. https://doi.org/10.1038/nrd3295
Sadae W, Yu VC, Richards ML et al (1987) Expression of neurotransmitter receptors and myc protooncogenes in subclones of a human neuroblastoma cell line. Cancer Res 47:5092–5140
Sanguinetti MC, Tristani-Firouzi M (2006) hERG potassium channels and cardiac arrhythmia. Nature 440:463–469. https://doi.org/10.1038/nature04710
Schaub S, Wilkins JA, Antonovici M, Krokhin O, Weiler T, Rush DNP (2005) Proteomic- based identification of cleaved urinary β2-microglobulin as a potential marker for acute tubular injury in renal allografts. Am J Transplant 5:729–738
Schildknecht S, Pöltl D, Nagel DM et al (2009) Requirement of a dopaminergic neuronal phenotype for toxicity of low concentrations of 1-methyl-4-phenylpyridinium to human cells. Toxicol Appl Pharmacol 241:23–35. https://doi.org/10.1016/j.taap.2009.07.027
Schoonen WG, De Roos JA, Westerink WMDE (2005a) Cytotoxic effects of 110 reference compounds on HepG2 cells and for 60 compounds on HeLa, ECC-1 and CHO cells.: II Mechanistic assays on NAD (P) H, ATP and DNA contents. Toxicol Vitr 19:491–503
Schoonen WG, Westerink WM, de Roos JADE (2005b) Cytotoxic effects of 100 reference compounds on Hep G2 and HeLa cells and of 60 compounds on ECC-1 and CHO cells. I mechanistic assays on ROS, glutathione depletion and calcein uptake. Toxicol Vitr 19:505–516
Schubert D, LaCorbiere M, Klier FG, Steinbach JH (1980) The modulation of neurotransmitter synthesis by steroid hormones and insulin. Brain Res 190:67–79. https://doi.org/10.1016/0006-8993(80)91160-9
Schutgens F, Rookmaaker MB, Margaritis T et al (2019) Tubuloids derived from human adult kidney and urine for personalized disease modeling. Nat Biotechnol 37:303–313. https://doi.org/10.1038/s41587-019-0048-8
Secker PF, Luks L, Schlichenmaier N, Dietrich DR (2018) RPTEC/TERT1 cells form highly differentiated tubules when cultured in a 3D matrix. ALTEX 35:223–234. https://doi.org/10.14573/altex.1710181
Shao C, Li M, Li X et al (2011) A tool for biomarker discovery in the urinary proteome: A manually curated human and animal urine protein biomarker database. Mol Cell Proteomics 10:1–9. https://doi.org/10.1074/mcp.M111.010975
Shastry P, Basu A, Rajadhyaksha M (2001) Neuroblastoma cell lines-A versatile in vitro model in neurobiology. Int J Neurosci 108:109–126
Shen G, Shen F, Shi Z et al (2008) Identification of cancer stem-like cells in the C6 glioma cell line and the limitation of current identification methods. Vitr Cell Dev Biol Anim 44:280–289. https://doi.org/10.1007/s11626-008-9115-z
Simon-Friedt BR, Wilson MJ, Blake DA, Yu H, Eriksson YWJ (2015) The RPTEC/TERT1 cell line as an improved tool for in-vitro nephrotoxicity assessments. Biol Trace Elem Res 166:66–71. https://doi.org/10.1007/s12011-015-0339-y.The
Singer P (1975) Animal liberation: a new ethics for our treatment of animals. House, Random, New York
Sjögren AK, Breitholtz K, Ahlberg E et al (2018) A novel multi-parametric high content screening assay in ciPTEC-OAT1 to predict drug-induced nephrotoxicity during drug discovery. Arch Toxicol 92:3175–3190. https://doi.org/10.1007/s00204-018-2284-y
Sleno L, Varesio E, Hopfgartner G (2007) Determining protein adducts of fipexide: mass spectrometry based assay for confirming the involvement of its reactive metabolite in covalent binding. Rapid Commun Mass Spectrom. An Int J Devoted to Rapid Dissem Up-to-the-Minute Res Mass Spectrom 21:4149–4157
Smith AJ, Stone TW, Smith RA (2008) Preconditioning with NMDA protects against toxicity of 3-nitropropionic acid or glutamate in cultured cerebellar granule neurons. Neurosci Lett 440:294–298. https://doi.org/10.1016/j.neulet.2008.05.066
Söderström S, Ebendal T (1995) In-vitro toxicity of methyl mercury: effects on nerve growth factor (NGF)-responsive neurons and on NGF synthesis in fibroblasts. Toxicol Lett 75:133–144. https://doi.org/10.1016/0378-4274(94)03176-8
Soldatow VY, Lecluyse EL, Griffith LG, Rusyn I (2013) In-vitro models for liver toxicity testing. Toxicol Res (Camb) 2:23–39. https://doi.org/10.1039/c2tx20051a
de Sousa C, Lopes SM (2019) Accelerating maturation of kidney organoids. Nat Mater 18:303–304. https://doi.org/10.1038/s41563-019-0326-3
Suñol C, Babot Z, Fonfría E, Galofré M, Garcia D, Herrera N, Iraola SVI (2008) Studies with neuronal cells: from basic studies of mechanisms of neurotoxicity to the prediction of chemical toxicity. Toxicol Vitr 22:1350–1355
Takasato M, Er PX, Chiu HS et al (2015) Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature 526:564–568. https://doi.org/10.1038/nature15695
Tencer J, Bakoush O, Torffvit O (2000) Diagnostic and prognostic significance of proteinuria selectivity index in glomerular diseases. Clin Chim Acta 297:73–83. https://doi.org/10.1016/S0009-8981(00)00235-7
Teunissen CE, Khalil M (2012) Neurofilaments as biomarkers in multiple sclerosis. https://doi.org/10.1177/1352458512443092
Tirmenstein MA, Hu CX, Scicchitano MS et al (2005) Effects of 6-hydroxydopamine on mitochondrial function and glutathione status in SH-SY5Y human neuroblastoma cells. Toxicol Vitr 19:471–479. https://doi.org/10.1016/j.tiv.2005.01.006
Tirmenstein MA, Nicholls-Grzemski FA, Schmittgen TD et al (2000) Characterization of nitric oxide production following isolation of rat hepatocytes. Toxicol Sci 53:56–62. https://doi.org/10.1093/toxsci/53.1.56
Tong V, Teng XW, Chang TKH, Abbott FS (2005) Valproic acid II: Effects on oxidative stress, mitochondrial membrane potential, and cytotoxicity in glutathione-depleted rat hepatocytes. Toxicol Sci 86:436–443. https://doi.org/10.1093/toxsci/kfi185
Toutain HJ, Moronvalle-Halley V, Sarsat JP et al (1998) Morphological and functional integrity of precision-cut rat liver slices in rotating organ culture and multiwell plate culture: Effects of oxygen tension. Cell Biol Toxicol 14:175–190. https://doi.org/10.1023/A:1007458408863
Tsushima J, Nishimura K, Tashiro N et al (2012) Protective effect of planarian DJ-1 against 6-hydroxydopamine-induced neurotoxicity. Neurosci Res 74:277–283. https://doi.org/10.1016/j.neures.2012.09.003
Tumani H, Hartung HP, Hemmer B et al (2009) Cerebrospinal fluid biomarkers in multiple sclerosis. Neurobiol Dis 35:117–127. https://doi.org/10.1016/j.nbd.2009.04.010
Tuschl G, Lauer B, Mueller SO (2008) Primary hepatocytes as a model to analyze species-specific toxicity and drug metabolism. Expert Opin Drug Metab Toxicol 4:855–870. https://doi.org/10.1517/17425255.4.7.855
Ulrich RG, Bacon JA, Brass EP, Cramer CT, Petrella DK, Sun EL (2001) Metabolic, idiosyncratic toxicity of drugs: overview of the hepatic toxicity induced by the anxiolytic, Panadiplon. Chem Biol Interact 134:251–270
Vaidya VS, Ramirez V, Ichimura T et al (2006) Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Ren Physiol 290:517–529. https://doi.org/10.1152/ajprenal.00291.2005
Vale C, Pomés A, Rodríguez-Farré E, Suñol C (1997) Allosteric interactions between γ-aminobutyric acid, benzodiazepine and picrotoxinin binding sites in primary cultures of cerebellar granule cells. Differential effects induced by γ- and δ-hexachlorocyclohexane. Eur J Pharmacol 319:343–353. https://doi.org/10.1016/S0014-2999(96)00866-7
Vriend J, Nieskens TTG, Vormann MK et al (2018) Screening of drug-transporter interactions in a 3D microfluidic renal proximal tubule on a chip. AAPS J 20. https://doi.org/10.1208/s12248-018-0247-0
Wada T, Yokoyama H, Tomosugi N et al (1994) Detection of urinary interleukin-8 in glomerular diseases. Kidney Int 46:455–460. https://doi.org/10.1038/ki.1994.293
Wan HI, Soares H, Waring J (2012) Use of cerebrospinal fluid biomarkers in clinical trials for schizophrenia and depression. Biomark Med 6:119–129
Wang H, Gao X, Fukumoto S et al (1998) Post-isolation inducible nitric oxide synthase gene expression due to collagenase buffer perfusion and characterization of the gene regulation in primary cultured murine hepatocytes. J Biochem 124:892–899. https://doi.org/10.1093/oxfordjournals.jbchem.a022204
Waring MJ, Arrowsmith J, Leach AR et al (2015) An analysis of the attrition of drug candidates from four major pharmaceutical companies. Nat Rev Drug Discov 14:475–486. https://doi.org/10.1038/nrd4609
Weinstein DE (1997) Isolation and purification of primary rodent astrocytes. Curr Protoc Neurosci 00:1–9. https://doi.org/10.1002/0471142301.ns0305s00
Weinstein DE, Wu R (1999) Isolation and purification of primary Schwann cells. Curr Protoc Neurosci 8:1–9. https://doi.org/10.1002/0471142301.ns0317s08
Westerink RHEA (2008) The PC12 cell as model for neurosecretion. Acta Physiol 192:273–285. https://doi.org/10.1111/j.1748-1716.2007.01805.x.The
Wilmer MJ, Saleem MA, Masereeuw R et al (2010) Novel conditionally immortalized human proximal tubule cell line expressing functional influx and efflux transporters. Cell Tissue Res 339:449–457. https://doi.org/10.1007/s00441-009-0882-y
Woolf CJ, Reynolds ML, Molander C et al (1990) The growth-associated protein gap-43 appears in dorsal root ganglion cells and in the dorsal horn of the rat spinal cord following peripheral nerve injury. Neuroscience 34:465–478. https://doi.org/10.1016/0306-4522(90)90155-W
Wooster R, Ebner T, Sutherland L et al (1993) Drug and xenobiotic glucuronidation catalysed by cloned human liver UDP-Glucuronosyltransferases stably expressed in tissue culture cell lines. Toxicology 82:119–129. https://doi.org/10.1016/0300-483X(93)02607-I
Worboys PD, Bradbury A, Houston JB (1996) Kinetics of drug metabolism in rat liver slices. II. Comparison of clearance by liver slices and freshly isolated hepatocytes. Drug Metab Dispos 24:676–681
Wu Y, Yang L, Su T et al (2010) Pathological significance of a panel of urinary biomarkers in patients with drug-induced tubulointerstitial nephritis. Clin J Am Soc Nephrol 5:1954–1959. https://doi.org/10.2215/CJN.02370310
Xu F, Farkas S, Kortbeek S et al (2012) Mercury-induced toxicity of rat cortical neurons is mediated through N-methyl-DAspartate receptors. Mol Brain 5:1–14
Xu J, Ma M, Purcell WM (2003) Characterisation of some cytotoxic endpoints using rat liver and HepG2 spheroids as in-vitro models and their application in hepatotoxicity studies. II. Spheroid cell spreading inhibition as a new cytotoxic marker. Toxicol Appl Pharmacol 189:112–119. https://doi.org/10.1016/S0041-008X(03)00090-5
Xu JJ, Diaz D, O’Brien PJ (2004) Applications of cytotoxicity assays and pre-lethal mechanistic assays for assessment of human hepatotoxicity potential. Chem Biol Interact 150:115–128. https://doi.org/10.1016/j.cbi.2004.09.011
Xu SY, Pauksen K, Venge P (1995) Serum measurements of human neutrophil lipocalin (HNL) discriminate between acute bacterial and viral infections. Scand J Clin Lab Invest 55:125–131. https://doi.org/10.3109/00365519509089604
Yarmush MLKHDJ (1989) Hepatocyte geometry : sandwich function and extracellular culture in a matrix configuration. FASEB J 3:174–177
Ydens E, Lornet G, Smits V et al (2013) The neuroinflammatory role of Schwann cells in disease. Neurobiol Dis 55:95–103. https://doi.org/10.1016/j.nbd.2013.03.005
You F, Osawa Y, Hayaski SI, Nakashima S (2007) Immediate early gene IEX-1 induces astrocytic differentiation of U87-MG human glioma cells. J Cell Biochem 100:256–265. https://doi.org/10.1002/jcb.21082
Yu J, Vodyanik MA, Smuga-Otto K et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science (80- ) 318:1917–1920. https://doi.org/10.1126/science.1151526
Yuan H, Zhang W, Li H et al (2013) Neuroprotective effects of resveratrol on embryonic dorsal root ganglion neurons with neurotoxicity induced by ethanol. Food Chem Toxicol 55:192–201. https://doi.org/10.1016/j.fct.2012.12.052
Zbinden G (1987) Predictive value of animal studies in toxicology. CMR annual lecture centre for medicines research
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Shukla, V., Asthana, S., Tripathi, A. (2023). In Vitro Methodologies for the Safety Assessment of Drugs. In: Rajput, V.S., Runthala, A. (eds) Drugs and a Methodological Compendium . Springer, Singapore. https://doi.org/10.1007/978-981-19-7952-1_4
Download citation
DOI: https://doi.org/10.1007/978-981-19-7952-1_4
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-19-7951-4
Online ISBN: 978-981-19-7952-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)