Acetaminophen‐induced liver injury in obesity and nonalcoholic fatty liver disease

Liver International - Tập 34 Số 7 - 2014
Anaïs Michaut1, Caroline Moreau2,2, Marie‐Anne Robin1, Bernard Fromenty1
1INSERM, U991, Université de Rennes 1, Rennes, France
2Laboratoire de Biochimie et Toxicologie CHU Pontchaillou Rennes France

Tóm tắt

AbstractAlthough acetaminophen (APAP) is usually considered as a safe drug, this painkiller can lead to acute liver failure after overdoses. Moreover, there is evidence that the maximum recommended dosage can induce hepatic cytolysis in some individuals. Several predisposing factors appear to enhance the risk and severity of APAP‐induced liver injury including chronic alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions linked to obesity. In contrast, obesity by itself does not seem to be associated with a higher risk of APAP‐induced liver injury. Since 1987, seven studies dealt with APAP‐induced hepatotoxicity in rodent models of NAFLD and five of them found that this liver disease was associated with higher APAP toxicity. Unfortunately, these studies did not unequivocally established the mechanism(s) whereby NAFLD could favour APAP hepatotoxicity, although some investigations suggested that pre‐existent induction of hepatic cytochrome P450 2E1 (CYP2E1) could play a significant role by increasing the generation of N‐acetyl‐p‐benzoquinone imine (NAPQI), the toxic metabolite of APAP. Moreover, pre‐existent mitochondrial dysfunction associated with NAFLD could also be involved. In contrast, some investigations suggested that factors that could reduce the risk and severity of APAP hepatotoxicity in obesity and NAFLD include higher hepatic APAP glucuronidation, reduced CYP3A4 activity and increased volume of body distribution. Thus, the occurrence and the outcome of APAP‐induced liver injury in an obese individual with NAFLD might depend on a delicate balance between metabolic factors that can be protective and others that favour large hepatic levels of NAPQI.

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Tài liệu tham khảo

10.1111/j.1365-2710.2009.01143.x

10.1111/j.1365-2125.2010.03819.x

10.1002/hep.26294

10.1136/bmj.d2218

10.1001/jama.296.1.87

10.1038/clpt.2009.240

10.1016/S0399-8320(04)95062-2

10.1111/j.1365-2036.2007.03503.x

10.1002/hep.22536

10.1016/j.cgh.2008.02.053

10.1136/bmj.c6764

10.1378/chest.105.2.408

10.1016/S0736-4679(02)00526-7

10.1016/j.cgh.2009.03.034

10.1101/gr.090241.108

10.1124/dmd.113.053546

10.1093/aje/kws448

10.1007/s00431-013-2157-6

10.1172/JCI24930

10.1002/hep.26226

10.1002/hep.23280

10.1016/j.clinre.2011.04.015

10.1007/978-3-642-00663-0_12

10.3109/03602532.2010.527984

10.1111/j.1478-3231.2011.02501.x

10.3109/03602532.2011.602688

10.1111/j.1365-2125.1980.tb01812.x

10.1073/pnas.81.5.1327

10.1124/dmd.106.012492

10.1074/jbc.271.20.12063

10.1016/0006-2952(93)90295-8

10.1016/S0887-2333(01)00011-X

10.1080/00498250802512830

10.1053/jhep.2003.50095

Abernethy DR, 1983, Enhanced glucuronide conjugation of drugs in obesity: studies of lorazepam, oxazepam, and acetaminophen, J Lab Clin Med, 101, 873

10.2165/11599410-000000000-00000

10.1124/dmd.112.050641

10.1074/jbc.273.28.17940

10.1124/dmd.30.4.446

10.1007/978-3-642-00663-0_10

10.1016/j.jhep.2013.04.024

10.1002/hep.22798

10.1016/j.cgh.2006.07.014

10.1097/01.mjt.0000434043.62372.00

10.1093/bja/aep322

10.1055/s-2001-12932

10.1152/ajpendo.00379.2007

10.1038/oby.2008.337

10.1038/nrgastro.2010.191

10.1111/j.1365-2613.2011.00793.x

10.1100/tsw.2007.117

10.1016/j.pharmthera.2012.11.004

10.1538/expanim.51.191

Corcoran GB, 1987, Obesity as a risk factor in drug‐induced organ injury: increased liver and kidney damage by acetaminophen in the obese overfed rat, J Pharmacol Exp Ther, 241, 921

Blouin RA, 1987, Phenobarbital induction and acetaminophen hepatotoxicity: resistance in the obese Zucker rodent, J Pharmacol Exp Ther, 243, 565

10.1080/10739680500383423

10.1152/ajpgi.00361.2009

10.1111/j.1440-1746.2011.06807.x

10.1124/jpet.112.193813

10.1016/j.taap.2008.02.031

10.1172/JCI8814

10.1194/jlr.M600198-JLR200

10.1038/labinvest.3700489

10.1016/j.jhep.2003.09.020

10.1016/0006-2952(87)90412-6

10.1016/j.tiv.2008.02.001

10.1006/bbrc.1999.0202

Bellward GD, 1988, Hepatic cytochrome P‐450j induction in the spontaneously diabetic BB rat, Mol Pharmacol, 33, 140

10.1038/nature06928

10.1194/jlr.M039669

10.1016/j.hepres.2005.09.020

10.1097/SLA.0b013e3181dbb572

10.1042/CS20030285

10.1053/jhep.2002.34943

10.1016/j.taap.2004.10.001

10.1002/hep.22578

10.1016/j.jhep.2012.05.019

10.1074/jbc.M708916200

10.1111/j.1365-2362.2008.01936.x

10.1124/jpet.109.161612

10.1053/jhep.2003.50342

10.1111/j.1478-3231.2007.01524.x

10.4067/S0716-97602008000100010

10.1097/MPG.0b013e3181f9b3a0

10.1124/dmd.111.039925

10.1093/jat/bks139

10.3109/07435808709023667

Chaudhary IP, 1993, Effect of genetic obesity and phenobarbital treatment on the hepatic conjugation pathways, J Pharmacol Exp Ther, 265, 1333

10.1124/dmd.112.048439

10.1007/s11095-006-0071-6

10.1016/j.cgh.2006.12.021

10.1002/j.1552-4604.1981.tb01768.x

10.1038/clpt.1982.111

10.1016/j.clinbiochem.2012.03.024

10.1016/j.tiv.2010.11.019

10.1053/j.gastro.2008.09.011

10.1006/excr.1998.4120

10.1016/j.lfs.2006.06.046

10.1016/j.jhep.2012.12.018

10.1016/j.cld.2013.09.015

10.1002/hep.24290

10.1002/hep.22074

10.1124/jpet.109.155168

10.1111/j.1476-5381.2011.01580.x

10.1016/j.ajpath.2012.06.013

10.1053/j.gastro.2003.09.019

10.1194/jlr.M001602

10.1111/j.1440-1746.1990.tb01626.x

10.1002/hep.20949

10.1016/j.hepres.2006.07.009

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Liver International

Tập 34 Số 7

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