Genetic and Epigenetic Basis of Drug-Induced Liver Injury

Snigdha Singh; P.V.S.N. Kiran Kumar; J. Pradeep Kumar; Sojit Tomo; Dharamveer Yadav; Praveen Sharma; Mahadev Rao; Mithu Banerjee

doi:10.1055/a-2097-0531

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2023; 43(02): 163-175
DOI: 10.1055/a-2097-0531

Review Article

Genetic and Epigenetic Basis of Drug-Induced Liver Injury

Snigdha Singh

¹Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

,

P.V.S.N. Kiran Kumar

¹Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

,

J. Pradeep Kumar

¹Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

,

Sojit Tomo

¹Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

,

Dharamveer Yadav

¹Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

,

Praveen Sharma

¹Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

,

Mahadev Rao

²Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka, India

,

Mithu Banerjee

¹Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

› Author Affiliations

Abstract

Drug-induced liver injury (DILI) is a rare but severe adverse drug reaction seen in pharmacotherapy and a major cause of postmarketing drug withdrawals. Advances in genome-wide studies indicate that genetic and epigenetic diversity can lead to inter-individual differences in drug response and toxicity. It is necessary to identify how the genetic variations, in the presence of environmental factors, can contribute to development and progression of DILI. Studies on microRNA, histone modification, DNA methylation, and single nucleotide polymorphisms related to DILI were retrieved from databases and were analyzed for the current research and updated to develop this narrative review. We have compiled some of the major genetic, epigenetic, and pharmacogenetic factors leading to DILI. Many validated genetic risk factors of DILI, such as variants of drug-metabolizing enzymes, HLA alleles, and some transporters were identified. In conclusion, these studies provide useful information in risk alleles identification and on implementation of personalized medicine.

Keywords

drug-induced liver injury (DILI) - miRNA - DNA methylation - histone modifications - single nucleotide polymorphisms

Full Text

References

References
1 Shao Q, Mao X, Zhou Z, Huai C, Li Z. Research progress of pharmacogenomics in drug-induced liver injury. Front Pharmacol 2021; 12: 735260
2 Stephens C, Andrade RJ. Genetic predisposition to drug-induced liver injury. Clin Liver Dis 2020; 24 (01) 11-23
3 Leise MD, Poterucha JJ, Talwalkar JA. Drug-induced liver injury. Mayo Clin Proc 2014; 89 (01) 95-106
4 Bizzaro D, Crescenzi M, Liddo DR, Arcidiacono D, Cappon A, Bertalot T. et al. Sex dependant differences in inflammatory responses during liver regeneration in a murine model of Acute Liver Injury. Clin Sci 2018; 132 (02) 255-272
5 Sutti S, Tacke F. Liver inflammation and regeneration in drug-induced liver injury: sex matters!. Clin Sci (Lond) 2018; 132 (05) 609-613
6 Garcia-Cortes M, Robles-Diaz M, Stephens C, Ortega-Alonso A, Lucena MI, Andrade RJ. Drug induced liver injury: an update. Arch Toxicol 2020; 94 (10) 3381-3407
7 Suk KT, Kim DJ. Drug-induced liver injury: present and future. Clin Mol Hepatol 2012; 18 (03) 249-257
8 Kullak-Ublick GA, Andrade RJ, Merz M. et al. Drug-induced liver injury: recent advances in diagnosis and risk assessment. Gut 2017; 66 (06) 1154-1164
9 Fu S, Wu D, Jiang W. et al. Molecular biomarkers in drug-induced liver injury: challenges and future perspectives. Front Pharmacol 2020; 10: 1667
10 Fontana RJ, Watkins PB, Bonkovsky HL. et al; DILIN Study Group. Drug-Induced Liver Injury Network (DILIN) prospective study: rationale, design and conduct. Drug Saf 2009; 32 (01) 55-68
11 Villanueva-Paz M, Morán L, López-Alcántara N. et al. Oxidative stress in drug-induced liver injury (DILI): from mechanisms to biomarkers for use in clinical practice. Antioxidants 2021; 10 (03) 390
12 Hautekeete ML, Horsmans Y, Van Waeyenberge C. et al. HLA association of amoxicillin-clavulanate–induced hepatitis. Gastroenterology 1999; 117 (05) 1181-1186
13 Singer JB, Lewitzky S, Leroy E. et al. A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury. Nat Genet 2010; 42 (08) 711-714
14 Daly AK, Donaldson PT, Bhatnagar P. et al; DILIGEN Study, International SAE Consortium. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet 2009; 41 (07) 816-819
15 Kindmark A, Jawaid A, Harbron CG. et al. Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis. Pharmacogenomics J 2008; 8 (03) 186-195
16 Fontana RJ, Cirulli ET, Gu J. et al. The role of HLA-A*33:01 in patients with cholestatic hepatitis attributed to terbinafine. J Hepatol 2018; 69 (06) 1317-1325
17 Urban TJ, Nicoletti P, Chalasani N. et al; Drug-Induced Liver Injury Network (DILIN), Pharmacogenetics of Drug-Induced Liver Injury group (DILIGEN), International Serious Adverse Events Consortium (iSAEC). Minocycline hepatotoxicity: clinical characterization and identification of HLA-B*35:02 as a risk factor. J Hepatol 2017; 67 (01) 137-144
18 Singh H, Lata S, Nema V, Samani D, Ghate M, Gangakhedkar RR. CYP1A1m1 and CYP2C9*2 and *3 polymorphism and risk to develop ARV-associated hepatotoxicity and its severity. APMIS 2017; 125 (06) 523-535
19 Xiong S, Li L. The effect of CYP1A2 gene polymorphism on the metabolism of theophylline. Exp Ther Med 2018; 15 (01) 109-114
20 Yoon HY, Ahn MH, Yee J, Lee N, Han JM, Gwak HS. Influence of CYP2C9 and CYP2A6 on plasma concentrations of valproic acid: a meta-analysis. Eur J Clin Pharmacol 2020; 76 (08) 1053-1058
21 Zhao M, Zhang T, Li G, Qiu F, Sun Y, Zhao L. Associations of CYP2C9 and CYP2A6 polymorphisms with the concentrations of valproate and its hepatotoxin metabolites and valproate-induced hepatotoxicity. Basic Clin Pharmacol Toxicol 2017; 121 (02) 138-143
22 Yimer G, Amogne W, Habtewold A. et al. High plasma efavirenz level and CYP2B6*6 are associated with efavirenz-based HAART-induced liver injury in the treatment of naïve HIV patients from Ethiopia: a prospective cohort study. Pharmacogenomics J 2012; 12 (06) 499-506
23 Fricke-Galindo I, Céspedes-Garro C, Rodrigues-Soares F. et al. Interethnic variation of CYP2C19 alleles, ‘predicted’ phenotypes and ‘measured’ metabolic phenotypes across world populations. Pharmacogenomics J 2016; 16 (02) 113-123
24 Milosavljević F, Bukvić N, Pavlović Z. et al. Association of CYP2C19 and CYP2D6 poor and intermediate metabolizer status with antidepressant and antipsychotic exposure: a systematic review and meta-analysis. JAMA Psychiatry 2021; 78 (03) 270-280
25 Chavan BS, Kaur G, Gupta D, Aneja J. A prospective study to evaluate the effect of CYP2D6 polymorphism on plasma level of risperidone and its metabolite in north Indian patients with schizophrenia. Indian J Psychol Med 2018; 40 (04) 335-342
26 Koopmans AB, Braakman MH, Vinkers DJ, Hoek HW, van Harten PN. Meta-analysis of probability estimates of worldwide variation of CYP2D6 and CYP2C19. Transl Psychiatry 2021; 11 (01) 141
27 Jiang F, Yan H, Liang L. et al. Incidence and risk factors of anti-tuberculosis drug induced liver injury (DILI): large cohort study involving 4652 Chinese adult tuberculosis patients. Liver Int 2021; 41 (07) 1565-1575
28 Wang X, Wang W. Association between polymorphism of NUDT15 gene and hepatotoxicity induced by 6-MP in children with acute lymphoblastic leukemia [in Chinese]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021; 38 (12) 1258-1261
29 Lee SY, Sohn KM, Ryu JY, Yoon YR, Shin JG, Kim JW. Sequence-based CYP2D6 genotyping in the Korean population. Ther Drug Monit 2006; 28 (03) 382-387
30 Fang J, Bourin M, Baker GB. Metabolism of risperidone to 9-hydroxyrisperidone by human cytochromes P450 2D6 and 3A4. Naunyn Schmiedebergs Arch Pharmacol 1999; 359 (02) 147-151
31 Huang YS, Chern HD, Su WJ. et al. Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis. Hepatology 2003; 37 (04) 924-930
32 Toja-Camba FJ, Gesto-Antelo N, Maroñas O. et al. Review of pharmacokinetics and pharmacogenetics in atypical long-acting injectable antipsychotics. Pharmaceutics 2021; 13 (07) 935
33 Yoon Y, Park HD, Park KU, Kim JQ, Chang YS, Song J. Associations between CYP2E1 promoter polymorphisms and plasma 1,3-dimethyluric acid/theophylline ratios. Eur J Clin Pharmacol 2006; 62 (08) 627-631
34 Ercisli MF, Lechun G, Azeez SH, Hamasalih RM, Song S, Aziziaram Z. Relevance of genetic polymorphisms of the human cytochrome P450 3A4 in rivaroxaban-treated patients. Cell Mol Biomed Rep 2021; 1 (01) 33-41
35 Chen G, Wu SQ, Feng M. et al. Association of UGT2B7 polymorphisms with risk of induced liver injury by anti-tuberculosis drugs in Chinese Han. Int J Immunopathol Pharmacol 2017; 30 (04) 434-438
36 Hao J-Q, Chen Y, Li S-M. et al. Relationship between the polymorphisms of UGT1A6 genes and anti-tuberculosis drug induced hepatic-injury [in Chinese]. Chin J Hepatol 2011; 19 (03) 201-204
37 Stephens C, Lucena MI, Andrade RJ. Genetic risk factors in the development of idiosyncratic drug-induced liver injury. Expert Opin Drug Metab Toxicol 2021; 17 (02) 153-169
38 Alfirevic A, Pirmohamed M. Predictive genetic testing for drug-induced liver injury: considerations of clinical utility. Clin Pharmacol Ther 2012; 92 (03) 376-380
39 Daly AK, Aithal GP, Leathart JBS, Swainsbury RA, Dang TS, Day CP. Genetic susceptibility to diclofenac-induced hepatotoxicity: contribution of UGT2B7, CYP2C8, and ABCC2 genotypes. Gastroenterology 2007; 132 (01) 272-281
40 Eaton DL, Bammler TK. Concise review of the glutathione S-transferases and their significance to toxicology. Toxicol Sci 1999; 49 (02) 156-164
41 Buratti FM, Darney K, Vichi S. et al. Human variability in glutathione-S-transferase activities, tissue distribution and major polymorphic variants: meta-analysis and implication for chemical risk assessment. Toxicol Lett 2021; 337: 78-90
42 Leiro V, Fernández-Villar A, Valverde D. et al. Influence of glutathione S-transferase M1 and T1 homozygous null mutations on the risk of antituberculosis drug-induced hepatotoxicity in a Caucasian population. Liver Int 2008; 28 (06) 835-839
43 Simon T, Becquemont L, Mary-Krause M. et al. Combined glutathione-S-transferase M1 and T1 genetic polymorphism and tacrine hepatotoxicity. Clin Pharmacol Ther 2000; 67 (04) 432-437
44 Watanabe I, Tomita A, Shimizu M. et al. A study to survey susceptible genetic factors responsible for troglitazone-associated hepatotoxicity in Japanese patients with type 2 diabetes mellitus. Clin Pharmacol Ther 2003; 73 (05) 435-455
45 Marín F, García N, Muñoz X. et al. Simultaneous genotyping of GSTT1 and GSTM1 null polymorphisms by melting curve analysis in presence of SYBR Green I. J Mol Diagn 2010; 12 (03) 300-304
46 Wattanapokayakit S, Mushiroda T, Yanai H. et al. NAT2 slow acetylator associated with anti-tuberculosis drug-induced liver injury in Thai patients. Int J Tuberc Lung Dis 2016; 20 (10) 1364-1369
47 Penning TM, Su AL, El-Bayoumy K. Nitroreduction: a critical metabolic pathway for drugs, environmental pollutants, and explosives. Chem Res Toxicol 2022; 35 (10) 1747-1765
48 Hein DW. Molecular genetics and function of NAT1 and NAT2: role in aromatic amine metabolism and carcinogenesis. Mutat Res 2002; 506–507: 65-77
49 Sharma SK, Jha BK, Sharma A. et al. Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity. Indian J Med Res 2016; 144 (06) 924-928
50 Gonzalez FJ. Pharmacogenetics polymorphisms in xenobiotic metabolism. In: Arinç E, Schenkman JB, Hodgson E. eds. Molecular and Applied Aspects of Oxidative Drug Metabolizing Enzymes. NATO ASI Series. New York, NY: Springer US; 1999: 91-110
51 Du H, Chen X, Fang Y. et al. Slow N-acetyltransferase 2 genotype contributes to anti-tuberculosis drug-induced hepatotoxicity: a meta-analysis. Mol Biol Rep 2013; 40 (05) 3591-3596
52 Zhang M, Wang S, Wilffert B. et al. The association between the NAT2 genetic polymorphisms and risk of DILI during anti-TB treatment: a systematic review and meta-analysis. Br J Clin Pharmacol 2018; 84 (12) 2747-2760
53 Verma R, Patil S, Zhang N. et al. A rapid pharmacogenomic assay to detect NAT2 polymorphisms and guide isoniazid dosing for tuberculosis treatment. Am J Respir Crit Care Med 2021; 204 (11) 1317-1326
54 Li W, Chang N, Tian L. et al. miR-27b-3p, miR-181a-1-3p, and miR-326-5p are involved in the inhibition of macrophage activation in chronic liver injury. J Mol Med (Berl) 2017; 95 (10) 1091-1105
55 Sanjay S, Girish C. Role of miRNA and its potential as a novel diagnostic biomarker in drug-induced liver injury. Eur J Clin Pharmacol 2017; 73 (04) 399-407
56 Yokoi T, Oda S. Models of idiosyncratic drug-induced liver injury. Annu Rev Pharmacol Toxicol 2021; 61: 247-268
57 Li D, Tolleson WH, Yu D. et al. Regulation of cytochrome P450 expression by microRNAs and long noncoding RNAs: Epigenetic mechanisms in environmental toxicology and carcinogenesis. J Environ Sci Health Part C Environ Carcinog Ecotoxicol Rev 2019; 37 (03) 180-214
58 Chen K, Guo N, Zhang R, Wei C, Guo R. CYP2E1 and miRNA-378a-3p contribute to acetaminophen- or tripterygium glycosides-induced hepatotoxicity. Basic Clin Pharmacol Toxicol 2020; 126 (02) 153-165
59 Zhang T, Yang Z, Kusumanchi P, Han S, Liangpunsakul S. Critical role of microRNA-21 in the pathogenesis of liver diseases. Front Med (Lausanne) 2020; 7: 7
60 Li ZB, Chen DD, He QJ. et al. The LAC score indicates significant fibrosis in patients with chronic drug-induced liver injury: a large biopsy-based study. Front Pharmacol 2021; 12: 734090
61 Zheng J, Zhou H, Yang T. et al. Protective role of microRNA-31 in acetaminophen-induced liver injury: a negative regulator of c-Jun N-terminal kinase (JNK) signaling pathway. Cell Mol Gastroenterol Hepatol 2021; 12 (05) 1789-1807
62 López-Riera M, Conde I, Castell JV, Jover R. A novel MicroRNA signature for cholestatic drugs in human hepatocytes and its translation into novel circulating biomarkers for drug-induced liver injury patients. Toxicol Sci 2020; 173 (02) 229-243
63 Wang K, Zhang S, Marzolf B. et al. Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci U S A 2009; 106 (11) 4402-4407
64 Jarsiah P, Karami M, Nosrati A, Alizadeh A, Hashemi-Soteh MB. Circulating miR-122 and miR-192 as specific and sensitive biomarkers for drug-induced liver injury with acetaminophen in rats. Jundishapur J Nat Pharm Prod 2019; 14 (02)
65 Bakshi S, Kaur M, Saini N. et al. Altered expressions of circulating microRNAs 122 and 192 during antitubercular drug induced liver injury indicating their role as potential biomarkers. Hum Exp Toxicol 2021; 40 (09) 1474-1484
66 Liu Y, Li P, Liu L, Zhang Y. The diagnostic role of miR-122 in drug-induced liver injury: a systematic review and meta-analysis. Medicine (Baltimore) 2018; 97 (49) e13478
67 Yang Z, Wu W, Ou P. et al. MiR-122-5p knockdown protects against APAP-mediated liver injury through up-regulating NDRG3. Mol Cell Biochem 2021; 476 (02) 1257-1267
68 Kersaudy-Kerhoas M, Liga A, Roychoudhury A. et al. Microfluidic system for near-patient extraction and detection of miR-122 microRNA biomarker for drug-induced liver injury diagnostics. Biomicrofluidics 2022; 16 (02) 024108
69 Russo MW, Steuerwald N, Norton HJ. et al. Profiles of miRNAs in serum in severe acute drug induced liver injury and their prognostic significance. Liver Int 2017; 37 (05) 757-764
70 Li Y, Guo L, Hou Z, Gong H, Yan M, Zhang B. Role of MicroRNA-155 in triptolide-induced hepatotoxicity via the Nrf2-dependent pathway. J Ethnopharmacol 2021; 281: 114489
71 Yuan K, Zhang X, Lv L, Zhang J, Liang W, Wang P. Fine-tuning the expression of microRNA-155 controls acetaminophen-induced liver inflammation. Int Immunopharmacol 2016; 40: 339-346
72 Feng X, Bao J, Song C. et al. Functional role of miR–155 in physiological and pathological processes of liver injury (Review). Mol Med Rep 2021; 24 (04) 714
73 Blaya D, Aguilar-Bravo B, Hao F. et al. Expression of microRNA-155 in inflammatory cells modulates liver injury. Hepatology 2018; 68 (02) 691-706
74 Howard EW, Yang X. microRNA regulation in estrogen receptor-positive breast cancer and endocrine therapy. Biol Proced Online 2018; 20: 17
75 Wang X, He Y, Mackowiak B, Gao B. MicroRNAs as regulators, biomarkers and therapeutic targets in liver diseases. Gut 2021; 70 (04) 784-795
76 Gu J, Xu H, Chen Y, Li N, Hou X. MiR-223 as a regulator and therapeutic target in liver diseases. Front Immunol 2022; 13: 860661
77 Ye D, Zhang T, Lou G, Liu Y. Role of miR-223 in the pathophysiology of liver diseases. Exp Mol Med 2018; 50 (09) 1-12
78 Burgos-Aceves MA, Cohen A, Paolella G. et al. Modulation of mitochondrial functions by xenobiotic-induced microRNA: from environmental sentinel organisms to mammals. Sci Total Environ 2018; 645: 79-88
79 Mohr R, Özdirik B, Lambrecht J. et al. From liver cirrhosis to cancer: the role of micro-RNAs in hepatocarcinogenesis. Int J Mol Sci 2021; 22 (03) 1492
80 Endo S, Yano A, Fukami T, Nakajima M, Yokoi T. Involvement of miRNAs in the early phase of halothane-induced liver injury. Toxicology 2014; 319: 75-84
81 Jiang X, Li W, Tan M. et al. Identification of miRNAs involved in liver injury induced by chronic exposure to cadmium. Toxicology 2022; 469: 153133
82 Messner CJ, Premand C, Gaiser C, Kluser T, Kübler E, Suter-Dick L. Exosomal microRNAs release as a sensitive marker for drug-induced liver injury in vitro. Appl In Vitro Toxicol 2020; 6 (03) 77-89
83 Rupprechter SAE, Sloan DJ, Oosthuyzen W. et al. MicroRNA-122 and cytokeratin-18 have potential as a biomarkers of drug-induced liver injury in European and African patients on treatment for mycobacterial infection. Br J Clin Pharmacol 2021; 87 (08) 3206-3217
84 El Shaffei I, Abdel-Latif GA, Farag DB, Schaalan M, Salama RM. Ameliorative effect of betanin on experimental cisplatin-induced liver injury; the novel impact of miRNA-34a on the SIRT1/PGC-1α signaling pathway. J Biochem Mol Toxicol 2021; 35 (06) 1-14
85 TissueAtlas. . Accessed May 15, 2023 at: https://ccb-web.cs.uni-saarland.de/tissueatlas/patterns
86 Zhang B, Sun S, Shen L. et al. DNA methylation in the rat livers induced by low dosage isoniazid treatment. Environ Toxicol Pharmacol 2011; 32 (03) 486-490
87 Shen L, Zhang B, Sun S, Feng F. Methylation of cytochrome p450 2E1 promoter induced by low dosage of isoniazid. Environ Toxicol Pharmacol 2013; 36 (01) 149-151
88 Wei Y, Huai C, Zhou C. et al. A methylation functional detection hepatic cell system validates correlation between DNA methylation and drug-induced liver injury. Pharmacogenomics J 2020; 20 (05) 717-723
89 Deaton AM, Bird A. CpG islands and the regulation of transcription. Genes Dev 2011; 25 (10) 1010-1022
90 Zhang J, Zhu X, Li Y. et al. Correlation of CpG island methylation of the cytochrome P450 2E1/2D6 genes with liver injury induced by anti-tuberculosis drugs: a nested case-control study. Int J Environ Res Public Health 2016; 13 (08) 776
91 Jin B, Li Y, Robertson KD. DNA methylation: superior or subordinate in the epigenetic hierarchy?. Genes Cancer 2011; 2 (06) 607-617
92 Zhao H, Wang Y, Zhang T, Wang Q, Xie W. Drug-induced liver injury from anti-tuberculosis treatment: a retrospective cohort study. Med Sci Monit 2020; 26: e920350-e920351
93 Choudhury M, Park PH, Jackson D, Shukla SD. Evidence for the role of oxidative stress in the acetylation of histone H3 by ethanol in rat hepatocytes. Alcohol 2010; 44 (06) 531-540
94 Molla Y, Wubetu M, Dessie B. Anti-tuberculosis drug induced hepatotoxicity and associated factors among tuberculosis patients at selected hospitals, Ethiopia. Hepat Med 2021; 13: 1-8
95 Kovalenko VM, Bagnyukova TV, Sergienko OV. et al. Epigenetic changes in the rat livers induced by pyrazinamide treatment. Toxicol Appl Pharmacol 2007; 225 (03) 293-299
96 Huai C, Wei Y, Li M. et al. Genome-wide analysis of DNA methylation and antituberculosis drug-induced liver injury in the han chinese population. Clin Pharmacol Ther 2019; 106 (06) 1389-1397
97 Fromenty B. Inhibition of mitochondrial fatty acid oxidation in drug-induced hepatic steatosis. Liver Res 2019; 3 (03) 157-169
98 Lawrence JW, Darkin-Rattray S, Xie F, Neims AH, Rowe TC. 4-Quinolones cause a selective loss of mitochondrial DNA from mouse L1210 leukemia cells. J Cell Biochem 1993; 51 (02) 165-174
99 Lawrence JW, Claire DC, Weissig V, Rowe TC. Delayed cytotoxicity and cleavage of mitochondrial DNA in ciprofloxacin-treated mammalian cells. Mol Pharmacol 1996; 50 (05) 1178-1188
100 Igoudjil A, Begriche K, Pessayre D, Fromenty B. Mitochondrial, metabolic and genotoxic effects of antiretroviral nucleoside reverse-transcriptase inhibitors. Antiinfect Agents 2006; 5: 273-292
101 Fromenty B. Alteration of mitochondrial DNA homeostasis in drug-induced liver injury. Food Chem Toxicol 2020; 135: 110916
102 Prado F, Jimeno-González S, Reyes JC. Histone availability as a strategy to control gene expression. RNA Biol 2017; 14 (03) 281-286
103 Chen HP, Zhao YT, Zhao TC. Histone deacetylases and mechanisms of regulation of gene expression. Crit Rev Oncog 2015; 20 (1–2): 35-47
104 Krueger W, Boelsterli UA, Rasmussen TP. Stem cell strategies to evaluate idiosyncratic drug-induced liver injury. J Clin Transl Hepatol 2014; 2 (03) 143-152
105 Jiao F, Zhang Z, Hu H, Zhang Y, Xiong Y. SIRT6 activator UBCS039 inhibits thioacetamide-induced hepatic injury in vitro and in vivo. Front Pharmacol 2022; 13: 837544
106 Sinha S, Verma S, Chaturvedi MM. Differential expression of SWI/SNF chromatin remodeler subunits brahma and brahma-related gene during drug-induced liver injury and regeneration in mouse model. DNA Cell Biol 2016; 35 (08) 373-384