Abstract
Background: Liver injury induced by drugs has become a primary reason for acute liver disease and therefore posed a potential regulatory and clinical challenge over the past few decades and has gained much attention. It also remains the most common cause of failure of drugs during clinical trials. In 50% of all acute liver failure cases, drug-induced hepatoxicity is the primary factor and 5% of all hospital admissions.
Methods: The various hepatotoxins used to induce hepatotoxicity in experimental animals include paracetamol, CCl4, isoniazid, thioacetamide, erythromycin, diclofenac, alcohol, etc. Among the various models used to induce hepatotoxicity in rats, every hepatotoxin causes toxicity by different mechanisms.
Results: The drug-induced hepatotoxicity caused by paracetamol accounts for 39% of the cases and 13% hepatotoxicity is triggered by other hepatotoxic inducing agents.
Conclusion: Research carried out and the published papers revealed that hepatotoxins such as paracetamol and carbon- tetrachloride are widely used for experimental induction of hepatotoxicity in rats.
Keywords: Hepatotoxicity, hepatotoxins, liver damage, xenobiotics, cytochrome P450, lipopolysaccharide, liver toxicity.
[http://dx.doi.org/10.1056/NEJMra052270] [PMID: 16481640]
[http://dx.doi.org/10.1093/toxsci/kfh075] [PMID: 14976355]
[http://dx.doi.org/10.1016/j.yrtph.2009.03.003] [PMID: 19303041]
[http://dx.doi.org/10.1164/rccm.200510-1666ST] [PMID: 17021358]
[http://dx.doi.org/10.7326/0003-4819-137-12-200212170-00007] [PMID: 12484709]
[http://dx.doi.org/10.1111/j.1365-2036.2011.04674.x] [PMID: 21539586]
[http://dx.doi.org/10.1016/S1089-3261(05)70097-0] [PMID: 11232192]
[http://dx.doi.org/10.1002/hep.20215] [PMID: 15185301]
[http://dx.doi.org/10.2165/00002018-200124070-00001] [PMID: 11444721]
[http://dx.doi.org/10.1517/14740338.1.2.159] [PMID: 12904150]
[http://dx.doi.org/10.1016/S0041-008X(03)00368-5] [PMID: 14575648]
[http://dx.doi.org/10.1093/toxsci/65.2.166] [PMID: 11812920]
[http://dx.doi.org/10.1111/j.1365-2036.2007.03307.x] [PMID: 17451560]
[http://dx.doi.org/10.1016/j.jinf.2010.07.009] [PMID: 20670648]
[http://dx.doi.org/10.1016/j.cld.2007.06.009] [PMID: 17723919]
[http://dx.doi.org/10.1097/MPG.0b013e3181709464] [PMID: 18852631]
[http://dx.doi.org/10.1016/j.bjbas.2013.09.002]
[http://dx.doi.org/10.1111/j.1600-0404.2008.01009.x] [PMID: 18341684]
[http://dx.doi.org/10.1053/bean.2002.0265] [PMID: 12751547]
[http://dx.doi.org/10.1016/j.jep.2009.03.038] [PMID: 19501269]
[http://dx.doi.org/10.1111/apt.12109] [PMID: 23121117]
[http://dx.doi.org/10.1016/j.cld.2007.06.005] [PMID: 17723921]
[http://dx.doi.org/10.1007/s11739-012-0777-x] [PMID: 22477279]
[http://dx.doi.org/10.1016/S1532-0456(01)00237-X] [PMID: 11574291]
[http://dx.doi.org/10.1080/713611034] [PMID: 12708612]
[http://dx.doi.org/10.1016/S0002-9440(10)65594-0] [PMID: 9708811]
[http://dx.doi.org/10.1128/AAC.03925-14] [PMID: 25385104]
[http://dx.doi.org/10.1016/j.fct.2008.08.013] [PMID: 18783728]
[http://dx.doi.org/10.1371/journal.pone.0156090] [PMID: 27224286]
[http://dx.doi.org/10.1038/ijo.2013.116] [PMID: 23779049]
[http://dx.doi.org/10.1053/j.gastro.2009.09.015] [PMID: 19782079]
[http://dx.doi.org/10.1136/gutjnl-2013-305507] [PMID: 24037431]
[http://dx.doi.org/10.1126/scisignal.2005260] [PMID: 24894995]
[http://dx.doi.org/10.1055/s-0032-1301733]
[http://dx.doi.org/10.1007/978-3-642-00663-0_12]
[http://dx.doi.org/10.3109/03602532.2011.602688] [PMID: 22229890]
[http://dx.doi.org/10.1080/20014091111677] [PMID: 11215692]
[http://dx.doi.org/10.1006/taap.1996.8074] [PMID: 9073586]
[http://dx.doi.org/10.1007/978-1-4615-0667-6_99]
[http://dx.doi.org/10.1016/j.taap.2012.08.015] [PMID: 22980195]
[http://dx.doi.org/10.1016/j.taap.2015.03.019] [PMID: 25818599]
[http://dx.doi.org/10.1186/1471-230X-11-20] [PMID: 21401949]
[http://dx.doi.org/10.1007/s11095-013-1007-6] [PMID: 23462933]
[http://dx.doi.org/10.1016/j.taap.2013.03.026] [PMID: 23571099]
[http://dx.doi.org/10.1016/j.taap.2006.08.001] [PMID: 16979204]
[http://dx.doi.org/10.3109/00498254.2014.986250] [PMID: 25423287]
[PMID: 2913271]
[http://dx.doi.org/10.1016/0006-2952(90)90558-3] [PMID: 2200409]
[http://dx.doi.org/10.1124/dmd.30.4.446] [PMID: 11901099]
[http://dx.doi.org/10.1053/j.gastro.2006.01.033] [PMID: 16530510]
[http://dx.doi.org/10.1038/clpt.2008.190] [PMID: 18923390]
[http://dx.doi.org/10.1136/gut.2006.104372] [PMID: 17185352]
[http://dx.doi.org/10.1053/j.gastro.2015.12.019] [PMID: 26708719]
[http://dx.doi.org/10.1016/j.bbrc.2008.06.065] [PMID: 18586006]
[http://dx.doi.org/10.1053/j.gastro.2008.07.006] [PMID: 18700144]
[http://dx.doi.org/10.1177/0192623312447551] [PMID: 22623522]
[http://dx.doi.org/10.1016/j.fct.2015.04.014] [PMID: 25865938]
[http://dx.doi.org/10.1016/j.taap.2010.04.015] [PMID: 20423716]
[http://dx.doi.org/10.1074/jbc.M109.054999] [PMID: 20061376]
[http://dx.doi.org/10.1124/mol.112.079863] [PMID: 22918968]
[http://dx.doi.org/10.1002/hep.26625] [PMID: 23873604]
[http://dx.doi.org/10.1002/hep.26625] [PMID: 23873604]
[http://dx.doi.org/10.1038/cddis.2014.241] [PMID: 24901049]
[http://dx.doi.org/10.1053/gast.2001.28692] [PMID: 11677195]
[http://dx.doi.org/10.1172/JCI200318384] [PMID: 12697731]
[http://dx.doi.org/10.1016/S1542-3565(04)00344-1] [PMID: 15354273]
[http://dx.doi.org/10.1097/00008571-200403000-00006] [PMID: 15167706]
[http://dx.doi.org/10.1111/j.1440-1746.2009.05917.x] [PMID: 19682195]
[http://dx.doi.org/10.1097/FTD.0b013e31815bf4dc] [PMID: 18043486]
[http://dx.doi.org/10.1097/MOG.0b013e32801145c2] [PMID: 17133087]
[http://dx.doi.org/10.1111/j.1365-2036.2008.03782.x] [PMID: 19145729]
[http://dx.doi.org/10.1124/jpet.104.069286] [PMID: 15226385]
[http://dx.doi.org/10.3329/icpj.v1i9.11619]
[http://dx.doi.org/10.1053/j.gastro.2004.06.020] [PMID: 15362044]
[http://dx.doi.org/10.1016/j.taap.2005.06.021] [PMID: 16051291]
[http://dx.doi.org/10.1111/jgh.12516] [PMID: 24783247]
[PMID: 20203555]
[http://dx.doi.org/10.1111/j.1440-1746.2007.05207.x] [PMID: 17995946]
[http://dx.doi.org/10.1016/j.apsb.2016.07.014] [PMID: 27709007]
[http://dx.doi.org/10.1080/17474124.2016.1196133] [PMID: 27248313]
[http://dx.doi.org/10.1002/jat.3175] [PMID: 26095833]
[http://dx.doi.org/10.1038/clpt.2010.355] [PMID: 21412230]
[PMID: 15132840]
[http://dx.doi.org/10.1093/toxsci/kfu094] [PMID: 24848797]
[http://dx.doi.org/10.1007/s40495-018-0131-8] [PMID: 30464886]
[http://dx.doi.org/10.1016/j.toxicon.2006.05.012] [PMID: 16860833]
[http://dx.doi.org/10.1053/jhep.2000.16183] [PMID: 10960448]
[http://dx.doi.org/10.1016/S0041-0101(98)00128-7] [PMID: 9839682]
[http://dx.doi.org/10.1016/S0378-1097(03)00100-9] [PMID: 12644220]
[http://dx.doi.org/10.5433/1679-0359.2008v29n2p417]
[http://dx.doi.org/10.1177/019262339802600316] [PMID: 9608648]
[http://dx.doi.org/10.1128/MCB.18.11.6353] [PMID: 9774651]
[http://dx.doi.org/10.1002/hep.20205] [PMID: 15122773]
[http://dx.doi.org/10.1053/j.gastro.2006.11.023] [PMID: 17241877]
[http://dx.doi.org/10.1177/0192623311418680] [PMID: 21885874]
[PMID: 6408387]
[http://dx.doi.org/10.1021/tx3001658] [PMID: 22667464]
[http://dx.doi.org/10.1021/tx3002719] [PMID: 22867114]
[http://dx.doi.org/10.1016/j.phymed.2003.04.003] [PMID: 15330497]
[http://dx.doi.org/10.1016/j.jep.2004.12.016] [PMID: 15740890]
[PMID: 19774206]
[http://dx.doi.org/10.1016/j.biomaterials.2008.04.048] [PMID: 18501960]
[http://dx.doi.org/10.1016/j.tox.2004.12.003] [PMID: 15725512]
[http://dx.doi.org/10.1097/NRL.0b013e31815bb3b7] [PMID: 18090948]
[http://dx.doi.org/10.1517/17425250902911455] [PMID: 19409030]
[http://dx.doi.org/10.1093/toxsci/kfi184] [PMID: 15858223]
[http://dx.doi.org/10.1093/toxsci/kfq294] [PMID: 20861068]
[http://dx.doi.org/10.1016/j.taap.2011.03.004] [PMID: 21397622]
[http://dx.doi.org/10.3389/fmicb.2013.00334] [PMID: 24312084]
[http://dx.doi.org/10.1258/0007142001902888] [PMID: 10885115]
[http://dx.doi.org/10.1080/10408440591007278] [PMID: 16417034]
[http://dx.doi.org/10.2174/2212798410901020155] [PMID: 20653536]
[http://dx.doi.org/10.1016/j.etap.2013.08.015] [PMID: 24322620]
[http://dx.doi.org/10.1016/j.fct.2013.07.047] [PMID: 23907020]
[http://dx.doi.org/10.1158/1078-0432.CCR-04-0098] [PMID: 15297390]
[http://dx.doi.org/10.2131/jts.35.663] [PMID: 20930461]
[http://dx.doi.org/10.1016/S0891-5849(00)00413-5] [PMID: 11084283]
[http://dx.doi.org/10.3402/ljm.v5i0.4621] [PMID: 28156294]
[http://dx.doi.org/10.1021/tx960083q] [PMID: 8902272]
[http://dx.doi.org/10.1124/jpet.109.164541] [PMID: 20124411]
[http://dx.doi.org/10.1002/hep.26196] [PMID: 23238640]
[http://dx.doi.org/10.1002/hep.21425] [PMID: 17133481]
[http://dx.doi.org/10.1093/toxsci/kfp165] [PMID: 19633216]
[PMID: 2818932]
[http://dx.doi.org/10.1093/intimm/8.4.569] [PMID: 8671644]
[http://dx.doi.org/10.1002/hep.510270227] [PMID: 9462651]
[http://dx.doi.org/10.1016/j.cbi.2008.10.028] [PMID: 19014921]
[http://dx.doi.org/10.1182/blood-2008-05-078154] [PMID: 18725574]
[http://dx.doi.org/10.1016/j.proghi.2004.04.001] [PMID: 15354618]
[http://dx.doi.org/10.4049/jimmunol.181.4.2831] [PMID: 18684975]
[http://dx.doi.org/10.1038/ki.1986.125] [PMID: 3528611]