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

Liver International

Volumn 34, Issue 7, 2014, Pages e171-e179

  Michaut, Anaïs ^a   Moreau, Caroline ^a,b   Robin, Marie Anne ^a   Fromenty, Bernard ^a  

^a INSERM   (France)

^b PONTCHAILLOU UNIVERSITY HOSPITAL   (France)

Author keywords

Acetaminophen; Cytochrome P450 2E1; Fatty liver; Hepatotoxicity; Obesity; Steatosis

Indexed keywords

CYTOCHROME P450 2E1; CYTOCHROME P450 3A4; DRUG METABOLITE; N ACETYL 1,4 BENZOQUINONE IMINE; PARACETAMOL; BENZOQUINONE DERIVATIVE; CYTOCHROME P450 3A; IMINE; N-ACETYL-4-BENZOQUINONEIMINE;

ACUTE LIVER FAILURE; ALCOHOL LIVER DISEASE; BODY DISTRIBUTION; CYTOLYSIS; DISEASE ASSOCIATION; DISEASE PREDISPOSITION; DRUG GLUCURONIDATION; DRUG METABOLISM; HUMAN; LIVER DISEASE; LIVER INJURY; LIVER TOXICITY; METABOLITE; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; RECOMMENDED DRUG DOSE; REVIEW; ABDOMINAL OBESITY; ANIMAL; COMPLICATION; METABOLISM; MITOCHONDRION; MOUSE; NON-ALCOHOLIC FATTY LIVER DISEASE; PATHOLOGY; RAT; TOXIC HEPATITIS;

ACETAMINOPHEN; ANIMALS; BENZOQUINONES; CYTOCHROME P-450 CYP3A; DRUG-INDUCED LIVER INJURY; HUMANS; IMINES; MICE; MITOCHONDRIA; NON-ALCOHOLIC FATTY LIVER DISEASE; OBESITY, ABDOMINAL; RATS;

EID: 84904462459     PISSN: 14783223     EISSN: 14783231     Source Type: Journal    
DOI: 10.1111/liv.12514     Document Type: Review

References (110)

1. Toussaint K, Yang XC, Zielinski MA, et al. What do we (not) know about how paracetamol (acetaminophen) works? J Clin Pharm Ther 2010; 35: 617-38.
2. Craig DG, Bates CM, Davidson JS, et al. Overdose pattern and outcome in paracetamol-induced acute severe hepatotoxicity. Br J Clin Pharmacol 2011; 71: 273-82.
3. Antoine DJ, Dear JW, Lewis PS, et al. Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital. Hepatology 2013; 58: 777-87.
4. Ferner RE, Dear JW, Bateman DN. Management of paracetamol poisoning. BMJ 2011; 342: d2218.
5. Watkins PB, Kaplowitz N, Slattery JT, et al. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial. JAMA 2006; 296: 87-93.
6. Winnike JH, Li Z, Wright FA, et al. Use of pharmaco-metabonomics for early prediction of acetaminophen-induced hepatotoxicity in humans. Clin Pharmacol Ther 2010; 88: 45-51.
7. Biour M, Ben Salem C, Chazouillères O, et al. Drug-induced liver injury; fourteenth updated edition of the bibliographic database of liver injuries and related drugs. Gastroenterol Clin Biol 2004; 28: 720-59.
8. Watelet J, Laurent V, Bressenot A, et al. Toxicity of chronic paracetamol ingestion. Aliment Pharmacol Ther 2007; 26: 1543-4.
9. Nguyen GC, Sam J, Thuluvath PJ. Hepatitis C is a predictor of acute liver injury among hospitalizations for acetaminophen overdose in the United States: a nationwide analysis. Hepatology 2008; 48: 1336-41.
10. Myers RP, Shaheen AA, Li B, et al. Impact of liver disease, alcohol abuse, and unintentional ingestions on the outcomes of acetaminophen overdose. Clin Gastroenterol Hepatol 2008; 6: 918-25.
11. Claridge LC, Eksteen B, Smith A, et al. Acute liver failure after administration of paracetamol at the maximum recommended daily dose in adults. BMJ 2010; 341: c6764.
12. Nolan CM, Sandblom RE, Thummel KE, et al. Hepatotoxicity associated with acetaminophen usage in patients receiving multiple drug therapy for tuberculosis. Chest 1994; 105: 408-11.
13. Lane JE, Belson MG, Brown DK, et al. Chronic acetaminophen toxicity: a case report and review of the literature. J Emerg Med 2002; 23: 253-6.
14. Suzuki A, Yuen N, Walsh J, et al. Co-medications that modulate liver injury and repair influence clinical outcome of acetaminophen-associated liver injury. Clin Gastroenterol Hepatol 2009; 7: 882-8.
15. Harrill AH, Watkins PB, Su S, et al. Mouse population-guided resequencing reveals that variants in CD44 contribute to acetaminophen-induced liver injury in humans. Genome Res 2009; 19: 1507-15.
16. Court MH, Peter I, Hazarika S, et al. Candidate gene polymorphisms in patients with acetaminophen-induced acute liver failure. Drug Metab Dispos 2014; 42: 28-32.
17. Lazo M, Hernaez R, Eberhardt MS, et al. Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988-1994. Am J Epidemiol 2013; 178: 38-45.
18. Berardis S, Sokal E. Pediatric non-alcoholic fatty liver disease: an increasing public health issue. Eur J Pediatr 2014; 173: 131-9.
19. Tamura S, Shimomura I. Contribution of adipose tissue and de novo lipogenesis to nonalcoholic fatty liver disease. J Clin Invest 2005; 115: 1139-42.
20. Begriche K, Massart J, Robin MA, et al. Mitochondrial adaptations and dysfunctions in nonalcoholic fatty liver disease. Hepatology 2013; 58: 1497-507.
21. Fabbrini E, Sullivan S, Klein S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology 2010; 51: 679-89.
22. Aubert J, Begriche K, Knockaert L, et al. Increased expression of cytochrome P450 2E1 in nonalcoholic fatty liver disease: mechanisms and pathophysiological role. Clin Res Hepatol Gastroenterol 2011; 35: 630-7.
23. Hinson JA, Roberts DW, James LP. Mechanisms of acetaminophen-induced liver necrosis. Handb Exp Pharmacol 2010; 196: 369-405.
24. Zhao L, Pickering G. Paracetamol metabolism and related genetic differences. Drug Metab Rev 2011; 43: 41-52.
25. Jaeschke H, Williams CD, Ramachandran A, et al. Acetaminophen hepatotoxicity and repair: the role of sterile inflammation and innate immunity. Liver Int 2012; 32: 8-20.
26. Jaeschke H, McGill MR, Ramachandran A. Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity. Drug Metab Rev 2012; 44: 88-106.
27. Prescott LF. Kinetics and metabolism of paracetamol and phenacetin. Br J Clin Pharmacol 1980; 10(Suppl 2): 291S-8S.
28. Dahlin DC, Miwa GT, Lu AY, et al. N-acetyl-p-benzoquinone imine: a cytochrome P450-mediated oxidation product of acetaminophen. Proc Natl Acad Sci USA 1984; 81: 1327-31.
29. Gonzalez FJ. The 2006 Bernard B. Brodie Award Lecture. Cyp2E1. Drug Metab Dispos 2007; 35: 1-8.
30. Lee SS, Buters JT, Pineau T, et al. Role of CYP2E1 in the hepatotoxicity of acetaminophen. J Biol Chem 1996; 271: 12063-7.
31. Thummel KE, Lee CA, Kunze KL, et al. Oxidation of acetaminophen to N-acetyl-p-aminobenzoquinone imine by human CYP3A4. Biochem Pharmacol 1993; 45: 1563-9.
32. Yoshitomi S, Ikemoto K, Takahashi J, et al. Establishment of the transformants expressing human cytochrome P450 subtypes in HepG2, and their applications on drug metabolism and toxicology. Toxicol In Vitro 2001; 15: 245-56.
33. Laine JE, Auriola S, Pasanen M, et al. Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes. Xenobiotica 2009; 39: 11-21.
34. Chalasani N, Gorski JC, Asghar MS, et al. Hepatic cytochrome P450 2E1 activity in nondiabetic patients with nonalcoholic steatohepatitis. Hepatology 2003; 37: 544-50.
35. Abernethy DR, Greenblatt DJ, Divoll M, et al. Enhanced glucuronide conjugation of drugs in obesity: studies of lorazepam, oxazepam, and acetaminophen. J Lab Clin Med 1983; 101: 873-80.
36. Brill MJ, Diepstraten J, van Rongen A, et al. Impact of obesity on drug metabolism and elimination in adults and children. Clin Pharmacokinet 2012; 51: 277-304.
37. Patoine D, Levac X, Pilote S, et al. Decreased CYP3A expression and activity in guinea pig models of diet-induced metabolic syndrome: is fatty liver infiltration involved? Drug Metab Dispos 2013; 41: 952-7.
38. Qiu Y, Benet LZ, Burlingame AL. Identification of the hepatic protein targets of reactive metabolites of acetaminophen in vivo in mice using two-dimensional gel electrophoresis and mass spectrometry. J Biol Chem 1998; 273: 17940-53.
39. Muldrew KL, James LP, Coop L, et al. Determination of acetaminophen-protein adducts in mouse liver and serum and human serum after hepatotoxic doses of acetaminophen using high-performance liquid chromatography with electrochemical detection. Drug Metab Dispos 2002; 30: 446-51.
40. Han D, Shinohara M, Ybanez MD, et al. Signal transduction pathways involved in drug-induced liver injury. Handb Exp Pharmacol 2010; 196: 267-310.
41. Uzi D, Barda L, Scaiewicz V, et al. CHOP is a critical regulator of acetaminophen-induced hepatotoxicity. J Hepatol 2013; 59: 495-503.
42. Myers RP, Shaheen AA. Hepatitis C alcohol abuse, and unintentional overdoses are risk factors for acetaminophen-related hepatotoxicity. Hepatology 2009; 49: 1399-400.
43. Rutherford A, Davern T, Hay JE, et al. Influence of high body mass index on outcome in acute liver failure. Clin Gastroenterol Hepatol 2006; 4: 1544-9.
44. Radosevich JJ, Patanwala AE, Erstad BL. Hepatotoxicity in obese versus nonobese patients with acetaminophen poisoning who are treated with intravenous N-acetylcysteine. Am J Ther 2013; doi: 10.1097/01.mjt.0000434043.62372.00 [Epub ahead of print].
45. Forget P, Wittebole X, Laterre PF. Therapeutic dose of acetaminophen may induce fulminant hepatitis in the presence of risk factors: a report of two cases. Br J Anaesth 2009; 103: 899-900.
46. Koteish A, Diehl AM. Animal models of steatosis. Semin Liver Dis 2001; 21: 89-104.
47. Begriche K, Lettéron P, Abbey-Toby A, et al. Partial leptin deficiency favors diet-induced obesity and related metabolic disorders in mice. Am J Physiol Endocrinol Metab 2008; 294: E939-51.
48. Begriche K, Massart J, Abbey-Toby A, et al. β-Aminoisobutyric acid prevents diet-induced obesity in mice with partial leptin deficiency. Obesity 2008; 16: 2053-67.
49. Hebbard L, George J. Animal models of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2011; 8: 35-44.
50. Trak-Smayra V, Paradis V, Massart J, et al. Pathology of the liver in obese and diabetic ob/ob and db/db mice fed a standard or high-calorie diet. Int J Exp Pathol 2011; 92: 413-21.
51. Lindström P. The physiology of obese-hyperglycemic mice [ob/ob mice]. ScientificWorldJournal 2007; 7: 666-85.
52. Fellmann L, Nascimento AR, Tibiriça E, et al. Murine models for pharmacological studies of the metabolic syndrome. Pharmacol Ther 2013; 137: 331-40.
53. Okazaki M, Saito Y, Udaka Y, et al. Diabetic nephropathy in KK and KK-Ay mice. Exp Anim 2002; 51: 191-6.
54. Corcoran GB, Wong BK. 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 1987; 241: 921-7.
55. Blouin RA, Dickson P, McNamara PJ, et al. Phenobarbital induction and acetaminophen hepatotoxicity: resistance in the obese Zucker rodent. J Pharmacol Exp Ther 1987; 243: 565-70.
56. Ito Y, Abril ER, Bethea NW, et al. Dietary steatotic liver attenuates acetaminophen hepatotoxicity in mice. Microcirculation 2006; 13: 19-27.
57. Kon K, Ikejima K, Okumura K, et al. Diabetic KK-A(y) mice are highly susceptible to oxidative hepatocellular damage induced by acetaminophen. Am J Physiol Gastrointest Liver Physiol 2010; 299: G329-37.
58. Kucera O, Rousar T, Stankova P, et al. Susceptibility of rat non-alcoholic fatty liver to the acute toxic effect of acetaminophen. J Gastroenterol Hepatol 2012; 27: 323-30.
59. Aubert J, Begriche K, Delannoy M, et al. Differences in early acetaminophen hepatotoxicity between obese ob/ob and db/db mice. J Pharmacol Exp Ther 2012; 342: 676-87.
60. Donthamsetty S, Bhave VS, Mitra MS, et al. Nonalcoholic steatohepatitic (NASH) mice are protected from higher hepatotoxicity of acetaminophen upon induction of PPARalpha with clofibrate. Toxicol Appl Pharmacol 2008; 230: 327-37.
61. Leclercq IA, Farrell GC, Field J, et al. CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis. J Clin Invest 2000; 105: 1067-75.
62. Rizki G, Arnaboldi L, Gabrielli B, et al. Mice fed a lipogenic methionine-choline-deficient diet develop hypermetabolism coincident with hepatic suppression of SCD-1. J Lipid Res 2006; 47: 2280-90.
63. Leclercq IA, Lebrun VA, Stärkel P, et al. Intrahepatic insulin resistance in a murine model of steatohepatitis: effect of PPARgamma agonist pioglitazone. Lab Invest 2007; 87: 56-65.
64. Rinella ME, Green RM. The methionine-choline deficient dietary model of steatohepatitis does not exhibit insulin resistance. J Hepatol 2004; 40: 47-51.
65. Tee LB, Davies DS, Seddon CE, et al. Species differences in the hepatotoxicity of paracetamol are due to differences in the rate of conversion to its cytotoxic metabolite. Biochem Pharmacol 1987; 36: 1041-52.
66. Jemnitz K, Veres Z, Monostory K, et al. Interspecies differences in acetaminophen sensitivity of human, rat, and mouse primary hepatocytes. Toxicol In Vitro 2008; 22: 961-7.
67. Enriquez A, Leclercq I, Farrell GC, et al. Altered expression of hepatic CYP2E1 and CYP4A in obese, diabetic ob/ob mice, and fa/fa Zucker rats. Biochem Biophys Res Commun 1999; 255: 300-6.
68. Bellward GD, Chang T, Rodrigues B, et al. Hepatic cytochrome P-450j induction in the spontaneously diabetic BB rat. Mol Pharmacol 1988; 33: 140-3.
69. Guo Y, Walther TC, Rao M, et al. Functional genomic screen reveals genes involved in lipid-droplet formation and utilization. Nature 2008; 453: 657-61.
70. Shi X, Li J, Zou X, et al. Regulation of lipid droplet size and phospholipid composition by stearoyl-CoA desaturase. J Lipid Res 2013; 54: 2504-14.
71. Seki S, Kitada T, Sakaguchi H. Clinicopathological significance of oxidative cellular damage in non-alcoholic fatty liver diseases. Hepatol Res 2005; 33: 132-4.
72. Bell LN, Temm CJ, Saxena R, et al. Bariatric surgery-induced weight loss reduces hepatic lipid peroxidation levels and affects hepatic cytochrome P450 protein content. Ann Surg 2010; 251: 1041-8.
73. Videla LA, Rodrigo R, Orellana M, et al. Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients. Clin Sci 2004; 106: 261-8.
74. Zhao P, Kalhorn TF, Slattery JT. Selective mitochondrial glutathione depletion by ethanol enhances acetaminophen toxicity in rat liver. Hepatology 2002; 36: 326-35.
75. Fernandez-Checa JC, Kaplowitz N. Hepatic mitochondrial glutathione: transport and role in disease and toxicity. Toxicol Appl Pharmacol 2005; 204: 263-73.
76. Singh R, Wang Y, Xiang Y, et al. Differential effects of JNK1 and JNK2 inhibition on murine steatohepatitis and insulin resistance. Hepatology 2009; 49: 87-96.
77. Abdelmegeed MA, Banerjee A, Yoo SH, et al. Critical role of cytochrome P450 2E1 (CYP2E1) in the development of high fat-induced non-alcoholic steatohepatitis. J Hepatol 2012; 57: 860-6.
78. Hanawa N, Shinohara M, Saberi B, et al. Role of JNK translocation to mitochondria leading to inhibition of mitochondria bioenergetics in acetaminophen-induced liver injury. J Biol Chem 2008; 283: 13565-77.
79. Serviddio G, Bellanti F, Tamborra R, et al. Alterations of hepatic ATP homeostasis and respiratory chain during development of non-alcoholic steatohepatitis in a rodent model. Eur J Clin Invest 2008; 38: 245-52.
80. Serviddio G, Bellanti F, Giudetti AM, et al. A silybin-phospholipid complex prevents mitochondrial dysfunction in a rodent model of nonalcoholic steatohepatitis. J Pharmacol Exp Ther 2010; 332: 922-32.
81. Emery MG, Fisher JM, Chien JY, et al. CYP2E1 activity before and after weight loss in morbidly obese subjects with nonalcoholic fatty liver disease. Hepatology 2003; 38: 428-35.
82. Chtioui H, Semela D, Ledermann M, et al. Expression and activity of the cytochrome P450 2E1 in patients with nonalcoholic steatosis and steatohepatitis. Liver Int 2007; 27: 764-71.
83. Varela NM, Quiñones LA, Orellana M, et al. Study of cytochrome P450 2E1 and its allele variants in liver injury of nondiabetic, nonalcoholic steatohepatitis obese women. Biol Res 2008; 41: 81-92.
84. Barshop NJ, Capparelli EV, Sirlin CB, et al. Acetaminophen pharmacokinetics in children with nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 2011; 52: 198-202.
85. Xu J, Kulkarni SR, Li L, et al. UDP-glucuronosyltransferase expression in mouse liver is increased in obesity and fasting-induced steatosis. Drug Metab Dispos 2012; 40: 259-66.
86. Gicquel T, Aubert J, Lepage S, et al. Quantitative analysis of acetaminophen and its primary metabolites in small plasma volumes by liquid chromatography-tandem mass spectrometry. J Anal Toxicol 2013; 37: 110-6.
87. Corcoran GB, Wong BK, Shum L, et al. Acetaminophen sulfation deficit in obese rats overfed an energy-dense cafeteria diet. Endocr Res 1987; 13: 101-21.
88. Chaudhary IP, Tuntaterdtum S, McNamara PJ, et al. Effect of genetic obesity and phenobarbital treatment on the hepatic conjugation pathways. J Pharmacol Exp Ther 1993; 265: 1333-8.
89. Hardwick RN, Ferreira DW, More VR, et al. Altered UDP-glucuronosyltransferase and sulfotransferase expression and function during progressive stages of human nonalcoholic fatty liver disease. Drug Metab Dispos 2013; 41: 554-61.
90. Yoshinari K, Takagi S, Yoshimasa T, et al. Hepatic CYP3A expression is attenuated in obese mice fed a high-fat diet. Pharm Res 2006; 23: 1188-200.
91. Kolwankar D, Vuppalanchi R, Ethell B, et al. Association between nonalcoholic hepatic steatosis and hepatic cytochrome P-450 3A activity. Clin Gastroenterol Hepatol 2007; 5: 388-93.
92. Lee WH, Kramer WG, Granville GE. The effect of obesity on acetaminophen pharmacokinetics in man. J Clin Pharmacol 1981; 21: 284-7.
93. Abernethy DR, Divoll M, Greenblatt DJ, et al. Obesity, sex, and acetaminophen disposition. Clin Pharmacol Ther 1982; 31: 783-90.
94. Grattagliano I, de Bari O, Bernardo TC, et al. Role of mitochondria in nonalcoholic fatty liver disease: from origin to propagation. Clin Biochem 2012; 45: 610-8.
95. Knockaert L, Descatoire V, Vadrot N, et al. Mitochondrial CYP2E1 is sufficient to mediate oxidative stress and cytotoxicity induced by ethanol and acetaminophen. Toxicol In Vitro 2011; 25: 475-84.
96. Chalasani N, Fontana RJ, Bonkovsky HL, et al. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135: 1924-34.
97. Oesch-Bartlomowicz B, Padma PR, Becker R, et al. Differential modulation of CYP2E1 activity by cAMP-dependent protein kinase upon Ser129 replacement. Exp Cell Res 1998; 242: 294-302.
98. Wauthier V, Schenten V, Verbeeck RK, et al. Ageing is associated with increased expression but decreased activity of CYP2E1 in male Wistar rats. Life Sci 2006; 79: 1913-20.
99. Fromenty B. Drug-induced liver injury in obesity. J Hepatol 2013; 58: 824-6.
100. Pais R, Rusu E, Ratziu V. The impact of obesity and metabolic syndrome on chronic hepatitis B and drug-induced liver disease. Clin Liver Dis 2014; 18: 165-78.
101. Anthérieu S, Rogue A, Fromenty B, et al. Induction of vesicular steatosis by amiodarone and tetracycline is associated with up-regulation of lipogenic genes in HepaRG cells. Hepatology 2011; 53: 1895-905.
102. Song Z, Zhou Z, Deaciuc I, et al. Inhibition of adiponectin production by homocysteine: a potential mechanism for alcoholic liver disease. Hepatology 2008; 47: 867-79.
103. Fromenty B, Vadrot N, Massart J, et al. Chronic ethanol consumption lessens the gain of body weight, liver triglycerides, and diabetes in obese ob/ob mice. J Pharmacol Exp Ther 2009; 331: 23-34.
104. Massart J, Robin MA, Noury F, et al. Pentoxifylline aggravates fatty liver in obese and diabetic ob/ob mice by increasing intestinal glucose absorption and activating hepatic lipogenesis. Br J Pharmacol 2012; 165: 1361-74.
105. Tan X, Sun X, Li Q, et al. Leptin deficiency contributes to the pathogenesis of alcoholic fatty liver disease in mice. Am J Pathol 2012; 181: 1279-86.
106. Carmiel-Haggai M, Cederbaum AI, Nieto N. Binge ethanol exposure increases liver injury in obese rats. Gastroenterology 2003; 125: 1818-33.
107. Cipriani S, Mencarelli A, Palladino G, et al. FXR activation reverses insulin resistance and lipid abnormalities and protects against liver steatosis in Zucker (fa/fa) obese rats. J Lipid Res 2010; 51: 771-84.
108. Zaluzny L, Farrell GC, Murray M. Effect of genetic obesity and experimental diabetes on hepatic microsomal mixed function oxidase activities. J Gastroenterol Hepatol 1990; 5: 256-63.
109. Robin MA, Demeilliers C, Sutton A, et al. Alcohol increases tumor necrosis factor-α and decreases nuclear factor-αB to activate hepatic apoptosis in genetically obese mice. Hepatology 2005; 42: 1280-90.
110. Okumura K, Ikejima K, Kon K, et al. Exacerbation of dietary steatohepatitis and fibrosis in obese, diabetic KK-A(y) mice. Hepatol Res 2006; 36: 217-28.