Toxicogenomic Biomarkers for Liver Toxicity

Overview

Journal J Toxicol Pathol

Date 2012 Jan 25

PMID 22271975

Citations 7

Authors

Naoki Kiyosawa

Yosuke Ando

Sunao Manabe

Takashi Yamoto

Affiliations

Soon will be listed here.

Abstract

Toxicogenomics (TGx) is a widely used technique in the preclinical stage of drug development to investigate the molecular mechanisms of toxicity. A number of candidate TGx biomarkers have now been identified and are utilized for both assessing and predicting toxicities. Further accumulation of novel TGx biomarkers will lead to more efficient, appropriate and cost effective drug risk assessment, reinforcing the paradigm of the conventional toxicology system with a more profound understanding of the molecular mechanisms of drug-induced toxicity. In this paper, we overview some practical strategies as well as obstacles for identifying and utilizing TGx biomarkers based on microarray analysis. Since clinical hepatotoxicity is one of the major causes of drug development attrition, the liver has been the best documented target organ for TGx studies to date, and we therefore focused on information from liver TGx studies. In this review, we summarize the current resources in the literature in regard to TGx studies of the liver, from which toxicologists could extract potential TGx biomarker gene sets for better hepatotoxicity risk assessment.

Citing Articles

High-Throughput Transcriptomics Differentiates Toxic versus Non-Toxic Chemical Exposures Using a Rat Liver Model.

Pannala V, Wallqvist A Int J Mol Sci. 2023; 24(24).

PMID: 38139254 PMC: 10743995. DOI: 10.3390/ijms242417425.

Emerging Bioinformatics Methods and Resources in Drug Toxicology.

Audouze K, Taboureau O Methods Mol Biol. 2022; 2425:133-146.

PMID: 35188631 DOI: 10.1007/978-1-0716-1960-5_6.

Identification of Translational microRNA Biomarker Candidates for Ketoconazole-Induced Liver Injury Using Next-Generation Sequencing.

Li D, Knox B, Gong B, Chen S, Guo L, Liu Z Toxicol Sci. 2020; 179(1):31-43.

PMID: 33078836 PMC: 7855383. DOI: 10.1093/toxsci/kfaa162.

Unsupervised identification of disease states from high-dimensional physiological and histopathological profiles.

Shimada K, Mitchison T Mol Syst Biol. 2019; 15(2):e8636.

PMID: 30782979 PMC: 6380462. DOI: 10.15252/msb.20188636.

Iron overload by Superparamagnetic Iron Oxide Nanoparticles is a High Risk Factor in Cirrhosis by a Systems Toxicology Assessment.

Wei Y, Zhao M, Yang F, Mao Y, Xie H, Zhou Q Sci Rep. 2016; 6:29110.

PMID: 27357559 PMC: 4928111. DOI: 10.1038/srep29110.

References

Coe K, Jia Y, Ho H, Rademacher P, Bammler T, Beyer R . Comparison of the cytotoxicity of the nitroaromatic drug flutamide to its cyano analogue in the hepatocyte cell line TAMH: evidence for complex I inhibition and mitochondrial dysfunction using toxicogenomic screening. Chem Res Toxicol. 2007; 20(9):1277-90. PMC: 2802183. DOI: 10.1021/tx7001349. View

Shao R, Hoshida Y, Otsuka M, Kato N, Tateishi R, Teratani T . Hepatic gene expression profiles associated with fibrosis progression and hepatocarcinogenesis in hepatitis C patients. World J Gastroenterol. 2005; 11(13):1995-9. PMC: 4305724. DOI: 10.3748/wjg.v11.i13.1995. View

Takahara Y, Takahashi M, Wagatsuma H, Yokoya F, Zhang Q, Yamaguchi M . Gene expression profiles of hepatic cell-type specific marker genes in progression of liver fibrosis. World J Gastroenterol. 2006; 12(40):6473-99. PMC: 4100637. DOI: 10.3748/wjg.v12.i40.6473. View

Kashida Y, Takahashi A, Moto M, Okamura M, Muguruma M, Jin M . Gene expression analysis in mice liver on hepatocarcinogenesis by flumequine. Arch Toxicol. 2006; 80(8):533-9. DOI: 10.1007/s00204-006-0065-5. View

Bleasby K, Castle J, Roberts C, Cheng C, Bailey W, Sina J . Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: a resource for investigations into drug disposition. Xenobiotica. 2006; 36(10-11):963-88. DOI: 10.1080/00498250600861751. View

Hamadeh H, Bushel P, Jayadev S, DiSorbo O, Bennett L, Li L . Prediction of compound signature using high density gene expression profiling. Toxicol Sci. 2002; 67(2):232-40. DOI: 10.1093/toxsci/67.2.232. View

Powell C, Kosyk O, Ross P, Schoonhoven R, Boysen G, Swenberg J . Phenotypic anchoring of acetaminophen-induced oxidative stress with gene expression profiles in rat liver. Toxicol Sci. 2006; 93(1):213-22. PMC: 1805881. DOI: 10.1093/toxsci/kfl030. View

Wu Y, Zhang X, Bardag-Gorce F, Robel R, Aguilo J, Chen L . Retinoid X receptor alpha regulates glutathione homeostasis and xenobiotic detoxification processes in mouse liver. Mol Pharmacol. 2004; 65(3):550-7. DOI: 10.1124/mol.65.3.550. View

Uehara T, Hirode M, Ono A, Kiyosawa N, Omura K, Shimizu T . A toxicogenomics approach for early assessment of potential non-genotoxic hepatocarcinogenicity of chemicals in rats. Toxicology. 2008; 250(1):15-26. DOI: 10.1016/j.tox.2008.05.013. View

10.

Burgoon L . The need for standards, not guidelines, in biological data reporting and sharing. Nat Biotechnol. 2006; 24(11):1369-73. DOI: 10.1038/nbt1106-1369. View

11.

Kanno J, Aisaki K, Igarashi K, Nakatsu N, Ono A, Kodama Y . "Per cell" normalization method for mRNA measurement by quantitative PCR and microarrays. BMC Genomics. 2006; 7:64. PMC: 1448209. DOI: 10.1186/1471-2164-7-64. View

12.

Auman J, Chou J, Gerrish K, Huang Q, Jayadev S, Blanchard K . Identification of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression in target and nontarget tissue. Environ Health Perspect. 2007; 115(4):572-8. PMC: 1852695. DOI: 10.1289/ehp.9396. View

13.

Slatter J, Cheng O, Cornwell P, de Souza A, Rockett J, Rushmore T . Microarray-based compendium of hepatic gene expression profiles for prototypical ADME gene-inducing compounds in rats and mice in vivo. Xenobiotica. 2006; 36(10-11):902-37. DOI: 10.1080/00498250600861694. View

14.

Inadera H, Tachibana S, Takasaki I, Tabuchi Y, Matsushima K, Uchida M . Expression profile of liver genes in response to hepatotoxicants identified using a SAGE-based customized DNA microarray system. Toxicol Lett. 2008; 177(1):20-30. DOI: 10.1016/j.toxlet.2007.12.004. View

15.

De Gottardi A, Vinciguerra M, Sgroi A, Moukil M, Ravier-DallAntonia F, Pazienza V . Microarray analyses and molecular profiling of steatosis induction in immortalized human hepatocytes. Lab Invest. 2007; 87(8):792-806. DOI: 10.1038/labinvest.3700590. View

16.

Kikkawa R, Fujikawa M, Yamamoto T, Hamada Y, Yamada H, Horii I . In vivo hepatotoxicity study of rats in comparison with in vitro hepatotoxicity screening system. J Toxicol Sci. 2006; 31(1):23-34. DOI: 10.2131/jts.31.23. View

17.

Dostalek M, Hardy K, Milne G, Morrow J, Chen C, Gonzalez F . Development of oxidative stress by cytochrome P450 induction in rodents is selective for barbiturates and related to loss of pyridine nucleotide-dependent protective systems. J Biol Chem. 2008; 283(25):17147-57. PMC: 2427356. DOI: 10.1074/jbc.M802447200. View

18.

Jiroutova A, Slavkovsky R, Cermakova M, Majdiakova L, Hanovcova I, Bolehovska R . Expression of mRNAs related to connective tissue metabolism in rat hepatic stellate cells and myofibroblasts. Exp Toxicol Pathol. 2006; 58(4):263-73. DOI: 10.1016/j.etp.2006.06.005. View

19.

Kiyosawa N, Uehara T, Gao W, Omura K, Hirode M, Shimizu T . Identification of glutathione depletion-responsive genes using phorone-treated rat liver. J Toxicol Sci. 2008; 32(5):469-86. DOI: 10.2131/jts.32.469. View

20.

Qiang H, Lin Y, Zhang X, Zeng X, Shi J, Chen Y . Differential expression genes analyzed by cDNA array in the regulation of rat hepatic fibrogenesis. Liver Int. 2006; 26(9):1126-37. DOI: 10.1111/j.1478-3231.2006.01353.x. View