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Article ; Online: The development and hepatotoxicity of acetaminophen: reviewing over a century of progress.

McGill, Mitchell R / Hinson, Jack A

2020 Volume 52, Issue 4, Page(s) 472–500

Abstract: Acetaminophen (APAP) was first synthesized in the 1800s, and came on the market approximately 65 years ago. Since then, it has become one of the most used drugs in the world. However, it is also a major cause of acute liver failure. Early investigations ... ...

Abstract	Acetaminophen (APAP) was first synthesized in the 1800s, and came on the market approximately 65 years ago. Since then, it has become one of the most used drugs in the world. However, it is also a major cause of acute liver failure. Early investigations of the mechanisms of toxicity revealed that cytochrome P450 enzymes catalyze formation of a reactive metabolite in the liver that depletes glutathione and covalently binds to proteins. That work led to the introduction of N-acetylcysteine (NAC) as an antidote for APAP overdose. Subsequent studies identified the reactive metabolite N-acetyl-
MeSH term(s)	Acetaminophen/metabolism ; Acetaminophen/toxicity ; Animals ; Chemical and Drug Induced Liver Injury/enzymology ; Chemical and Drug Induced Liver Injury/metabolism ; Cytochrome P-450 Enzyme System/metabolism ; Humans ; Liver/drug effects ; Liver/enzymology ; Liver/metabolism ; Oxidative Stress
Chemical Substances	Acetaminophen (362O9ITL9D) ; Cytochrome P-450 Enzyme System (9035-51-2)
Language	English
Publishing date	2020-10-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	184967-0
ISSN	1097-9883 ; 0360-2532 ; 0012-6594
ISSN (online)	1097-9883
ISSN	0360-2532 ; 0012-6594
DOI	10.1080/03602532.2020.1832112
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Article ; Online: Advances in biomarker development in acetaminophen toxicity.

James, Laura P / McGill, Mitchell R / Roberts, Dean W / Hinson, Jack A / Lee, William M

Advances in clinical chemistry

2020 Volume 98, Page(s) 35–50

Abstract: Acetaminophen liver injury is the most common cause of acute liver injury in the United States and several other countries. Diagnosis of acetaminophen-induced acute liver injury in the clinic is challenging due to the lack of validated and specific ... ...

Abstract	Acetaminophen liver injury is the most common cause of acute liver injury in the United States and several other countries. Diagnosis of acetaminophen-induced acute liver injury in the clinic is challenging due to the lack of validated and specific biomarkers. The following chapter provides an overview of recent advances evaluating candidate biomarkers in development for acetaminophen acute liver injury. Relationships of biomarkers to mechanisms of acetaminophen toxicity and their potential role in confirming the diagnosis and/or predicting evolving toxicity are addressed.
MeSH term(s)	Acetaminophen/adverse effects ; Acetaminophen/toxicity ; Animals ; Biomarkers/analysis ; Cell Death/drug effects ; Humans ; Inflammation/chemically induced ; Inflammation/pathology ; Liver/drug effects ; Liver/injuries ; Liver/metabolism ; Liver/pathology ; Mitochondria/drug effects
Chemical Substances	Biomarkers ; Acetaminophen (362O9ITL9D)
Language	English
Publishing date	2020-04-27
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	210505-6
ISSN	2162-9471 ; 0065-2423
ISSN (online)	2162-9471
ISSN	0065-2423
DOI	10.1016/bs.acc.2020.02.002
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Article: Trifluoperazine inhibits acetaminophen-induced hepatotoxicity and hepatic reactive nitrogen formation in mice and in freshly isolated hepatocytes.

Banerjee, Sudip / Melnyk, Stepan B / Krager, Kimberly J / Aykin-Burns, Nukhet / McCullough, Sandra S / James, Laura P / Hinson, Jack A

Toxicology reports

2016 Volume 4, Page(s) 134–142

Abstract: The hepatotoxicity of acetaminophen (APAP) occurs by initial metabolism to N-acetyl-p-benzoquinone imine which depletes GSH and forms APAP-protein adducts. Subsequently, the reactive nitrogen species peroxynitrite is formed from nitric oxide (NO) and ... ...

Abstract	The hepatotoxicity of acetaminophen (APAP) occurs by initial metabolism to N-acetyl-p-benzoquinone imine which depletes GSH and forms APAP-protein adducts. Subsequently, the reactive nitrogen species peroxynitrite is formed from nitric oxide (NO) and superoxide leading to 3-nitrotyrosine in proteins. Toxicity occurs with inhibited mitochondrial function. We previously reported that in hepatocytes the nNOS (NOS1) inhibitor NANT inhibited APAP toxicity, reactive nitrogen and oxygen species formation, and mitochondrial dysfunction. In this work we examined the effect of trifluoperazine (TFP), a calmodulin antagonist that inhibits calcium induced nNOS activation, on APAP hepatotoxicity and reactive nitrogen formation in murine hepatocytes and
Language	English
Publishing date	2016-10-13
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	2805786-7
ISSN	2214-7500
ISSN	2214-7500
DOI	10.1016/j.toxrep.2017.02.005
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Article: The spatial distribution of soil organic carbon in tidal wetland soils of the continental United States

Hinson, Audra L / Rusty A. Feagin / Marian Eriksson / Raymond G. Najjar / Maria Herrmann / Thomas S. Bianchi / Michael Kemp / Jack A. Hutchings / Steve Crooks / Thomas Boutton

Global change biology. 2017 Dec., v. 23, no. 12

2017

Abstract: Tidal wetlands contain large reservoirs of carbon in their soils and can sequester carbon dioxide (COâ) at a greater rate per unit area than nearly any other ecosystem. The spatial distribution of this carbon influences climate and wetland policy. To ... ...

Abstract	Tidal wetlands contain large reservoirs of carbon in their soils and can sequester carbon dioxide (COâ) at a greater rate per unit area than nearly any other ecosystem. The spatial distribution of this carbon influences climate and wetland policy. To assist with international accords such as the Paris Climate Agreement, nationalâlevel assessments such as the United States (U.S.) National Greenhouse Gas Inventory, and regional, state, local, and projectâlevel evaluation of COâ sequestration credits, we developed a geodatabase (CoBluCarb) and highâresolution maps of soil organic carbon (SOC) distribution by linking National Wetlands Inventory data with the U.S. Soil Survey Geographic Database. For over 600,000 wetlands, the total carbon stock and organic carbon density was calculated at 5âcm vertical resolution from 0 to 300Â cm of depth. Across the continental United States, there are 1,153â1,359 Tg of SOC in the upper 0â100Â cm of soils across a total of 24Â 945.9Â kmÂ² of tidal wetland area, twice as much carbon as the most recent national estimate. Approximately 75% of this carbon was found in estuarine emergent wetlands with freshwater tidal wetlands holding about 19%. The greatest pool of SOC was found within the Atchafalaya/Vermilion Bay complex in Louisiana, containing about 10% of the U.S. total. The average density across all tidal wetlands was 0.071Â g cmâ»Â³ across 0â15Â cm, 0.055Â g cmâ»Â³ across 0â100Â cm, and 0.040Â g cmâ»Â³ at the 100Â cm depth. There is inherent variability between and within individual wetlands; however, we conclude that it is possible to use standardized values at a range of 0â100Â cm of the soil profile, to provide firstâorder quantification and to evaluate future changes in carbon stocks in response to environmental perturbations. This Tier 2âoriented carbon stock assessment provides a scientific method that can be copied by other nations in support of international requirements.
Keywords	carbon dioxide ; carbon footprint ; carbon sequestration ; carbon sinks ; climate ; databases ; ecosystems ; estuaries ; freshwater ; inventories ; issues and policy ; soil organic carbon ; soil profiles ; soil surveys ; spatial data ; wetland soils ; wetlands ; Louisiana
Language	English
Dates of publication	2017-12
Size	p. 5468-5480.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	1281439-8
ISSN	1365-2486 ; 1354-1013
ISSN (online)	1365-2486
ISSN	1354-1013
DOI	10.1111/gcb.13811
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Article: Mechanisms of acetaminophen-induced liver necrosis.

Hinson, Jack A / Roberts, Dean W / James, Laura P

Handbook of experimental pharmacology

2009 , Issue 196, Page(s) 369–405

Abstract: Although considered safe at therapeutic doses, at higher doses, acetaminophen produces a centrilobular hepatic necrosis that can be fatal. Acetaminophen poisoning accounts for approximately one-half of all cases of acute liver failure in the United ... ...

Abstract	Although considered safe at therapeutic doses, at higher doses, acetaminophen produces a centrilobular hepatic necrosis that can be fatal. Acetaminophen poisoning accounts for approximately one-half of all cases of acute liver failure in the United States and Great Britain today. The mechanism occurs by a complex sequence of events. These events include: (1) CYP metabolism to a reactive metabolite which depletes glutathione and covalently binds to proteins; (2) loss of glutathione with an increased formation of reactive oxygen and nitrogen species in hepatocytes undergoing necrotic changes; (3) increased oxidative stress, associated with alterations in calcium homeostasis and initiation of signal transduction responses, causing mitochondrial permeability transition; (4) mitochondrial permeability transition occurring with additional oxidative stress, loss of mitochondrial membrane potential, and loss of the ability of the mitochondria to synthesize ATP; and (5) loss of ATP which leads to necrosis. Associated with these essential events there appear to be a number of inflammatory mediators such as certain cytokines and chemokines that can modify the toxicity. Some have been shown to alter oxidative stress, but the relationship of these modulators to other critical mechanistic events has not been well delineated. In addition, existing data support the involvement of cytokines, chemokines, and growth factors in the initiation of regenerative processes leading to the reestablishment of hepatic structure and function.
MeSH term(s)	Acetaminophen/adverse effects ; Acetaminophen/metabolism ; Analgesics, Non-Narcotic/adverse effects ; Analgesics, Non-Narcotic/metabolism ; Animals ; Biotransformation ; Chemical and Drug Induced Liver Injury/etiology ; Chemical and Drug Induced Liver Injury/metabolism ; Chemical and Drug Induced Liver Injury/pathology ; Chemokines/metabolism ; Cytokines/metabolism ; Humans ; Liver/blood supply ; Liver/drug effects ; Liver/metabolism ; Liver/pathology ; Liver Circulation/drug effects ; Liver Regeneration ; Mitochondria, Liver/drug effects ; Mitochondria, Liver/metabolism ; Mitochondria, Liver/pathology ; Necrosis ; Signal Transduction/drug effects
Chemical Substances	Analgesics, Non-Narcotic ; Chemokines ; Cytokines ; Acetaminophen (362O9ITL9D)
Language	English
Publishing date	2009-12-19
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ISSN	0171-2004
ISSN	0171-2004
DOI	10.1007/978-3-642-00663-0_12
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Article ; Online: The spatial distribution of soil organic carbon in tidal wetland soils of the continental United States.

Hinson, Audra L / Feagin, Rusty A / Eriksson, Marian / Najjar, Raymond G / Herrmann, Maria / Bianchi, Thomas S / Kemp, Michael / Hutchings, Jack A / Crooks, Steve / Boutton, Thomas

Global change biology

2017 Volume 23, Issue 12, Page(s) 5468–5480

Abstract: Tidal wetlands contain large reservoirs of carbon in their soils and can sequester carbon dioxide ( ... ...

Abstract	Tidal wetlands contain large reservoirs of carbon in their soils and can sequester carbon dioxide (CO
MeSH term(s)	Carbon/chemistry ; Ecosystem ; Environmental Monitoring ; Fresh Water ; Soil/chemistry ; Tidal Waves ; United States ; Wetlands
Chemical Substances	Soil ; Carbon (7440-44-0)
Language	English
Publishing date	2017-08-17
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1281439-8
ISSN	1365-2486 ; 1354-1013
ISSN (online)	1365-2486
ISSN	1354-1013
DOI	10.1111/gcb.13811
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Article ; Online: Reactive nitrogen species in acetaminophen-induced mitochondrial damage and toxicity in mouse hepatocytes.

Burke, Angela S / MacMillan-Crow, Lee Ann / Hinson, Jack A

Chemical research in toxicology

2010 Volume 23, Issue 7, Page(s) 1286–1292

Abstract: Acetaminophen (APAP) toxicity in primary mouse hepatocytes occurs in two phases. The initial phase (0-2 h) occurs with metabolism to N-acetyl-p-benzoquinoneimine which depletes glutathione, and covalently binds to proteins, but little toxicity is ... ...

Abstract	Acetaminophen (APAP) toxicity in primary mouse hepatocytes occurs in two phases. The initial phase (0-2 h) occurs with metabolism to N-acetyl-p-benzoquinoneimine which depletes glutathione, and covalently binds to proteins, but little toxicity is observed. Subsequent washing of hepatocytes to remove APAP and reincubating in media alone (2-5 h) results in toxicity. We previously reported that the reincubation phase occurs with mitochondrial permeability transition (MPT) and increased oxidative stress (dichlorodihydrofluorescein fluorescence) (DCFH(2)). Since DCFH(2) may be oxidized by multiple oxidative mechanisms, we investigated the role of reactive nitrogen species (RNS) leading to 3-nitrotyrosine in proteins by ELISA and by immunoblots. Incubation of APAP with hepatocytes for 2 h did not result in toxicity or protein nitration; however, washing hepatocytes and reincubating in media alone (2-5 h) resulted in protein nitration which correlated with toxicity. Inclusion of the MPT inhibitor, cyclosporine A, in the reincubation media eliminated toxicity and protein nitration. The general nitric oxide synthase (NOS) inhibitor L-NMMA and the neuronal NOS (NOS1) inhibitor, 7-nitroindazole, added in the reincubation media decreased toxicity and protein nitration; however, neither the inducible NOS (NOS2) inhibitors L-NIL (N6-(1-iminoethyl)-L-lysine) nor SAIT (S-(2-aminoethyl)isothiourea) decreased protein nitration or toxicity. The RNS scavengers, N-acetylcysteine, and high concentrations of APAP, added in the reincubation phase decreased toxicity and protein nitration. 7-Nitroindazole and cyclosporine A inhibited the APAP-induced loss of mitochondrial membrane potential when added in the reincubation phase. The data indicate a role for RNS in APAP induced toxicity.
MeSH term(s)	Acetaminophen/toxicity ; Animals ; Benzoquinones/metabolism ; Glutathione/metabolism ; Hepatocytes/drug effects ; Hepatocytes/metabolism ; Imines/metabolism ; Indazoles/chemistry ; Indazoles/pharmacology ; Lysine/analogs & derivatives ; Lysine/chemistry ; Lysine/pharmacology ; Mice ; Mitochondria/drug effects ; Oxidative Stress ; Reactive Nitrogen Species/metabolism
Chemical Substances	Benzoquinones ; Imines ; Indazoles ; N(6)-(1-iminoethyl)lysine ; Reactive Nitrogen Species ; Acetaminophen (362O9ITL9D) ; N-acetyl-4-benzoquinoneimine (G6S9BN13TI) ; Glutathione (GAN16C9B8O) ; Lysine (K3Z4F929H6) ; 7-nitroindazole (UX0N37CMVH)
Language	English
Publishing date	2010-06-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639353-6
ISSN	1520-5010 ; 0893-228X
ISSN (online)	1520-5010
ISSN	0893-228X
DOI	10.1021/tx1001755
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Article ; Online: The neuronal nitric oxide synthase inhibitor NANT blocks acetaminophen toxicity and protein nitration in freshly isolated hepatocytes.

Banerjee, Sudip / Melnyk, Stepan B / Krager, Kimberly J / Aykin-Burns, Nukhet / Letzig, Lynda G / James, Laura P / Hinson, Jack A

Free radical biology & medicine

2015 Volume 89, Page(s) 750–757

Abstract: 3-Nitrotyrosine (3NT) in liver proteins of mice treated with hepatotoxic doses of acetaminophen (APAP) has been postulated to be causative in toxicity. Nitration is by a reactive nitrogen species formed from nitric oxide (NO). The source of the NO is ... ...

Abstract	3-Nitrotyrosine (3NT) in liver proteins of mice treated with hepatotoxic doses of acetaminophen (APAP) has been postulated to be causative in toxicity. Nitration is by a reactive nitrogen species formed from nitric oxide (NO). The source of the NO is unclear. iNOS knockout mice were previously found to be equally susceptible to APAP toxicity as wildtype mice and iNOS inhibitors did not decrease toxicity in mice or in hepatocytes. In this work we examined the potential role of nNOS in APAP toxicity in hepatocytes using the specific nNOS inhibitor NANT (10 µM)(N-[(4S)-4-amino-5-[(2-aminoethyl)amino]pentyl]-N'-nitroguanidinetris (trifluoroacetate)). Primary hepatocytes (1 million/ml) from male B6C3F1 mice were incubated with APAP (1mM). Cells were removed and assayed spectrofluorometrically for reactive nitrogen and oxygen species using diaminofluorescein (DAF) and Mitosox red, respectively. Cytotoxicity was determined by LDH release into media. Glutathione (GSH, GSSG), 3NT, GSNO, acetaminophen-cysteine adducts, NAD, and NADH were measured by HPLC. APAP significantly increased cytotoxicity at 1.5-3.0 h. The increase was blocked by NANT. NANT did not alter APAP mediated GSH depletion or acetaminophen-cysteine adducts in proteins which indicated that NANT did not inhibit metabolism. APAP significantly increased spectroflurometric evidence of reactive nitrogen and oxygen formation at 0.5 and 1.0 h, respectively, and increased 3NT and GSNO at 1.5-3.0 h. These increases were blocked by NANT. APAP dramatically increased NADH from 0.5-3.0 h and this increase was blocked by NANT. Also, APAP decreased the Oxygen Consumption Rate (OCR), decreased ATP production, and caused a loss of mitochondrial membrane potential, which were all blocked by NANT.
MeSH term(s)	Acetaminophen/toxicity ; Analgesics, Non-Narcotic/toxicity ; Animals ; Chemical and Drug Induced Liver Injury/metabolism ; Chromatography, High Pressure Liquid ; Enzyme Inhibitors/pharmacology ; Guanidines/pharmacology ; Hepatocytes/drug effects ; Male ; Membrane Potential, Mitochondrial/drug effects ; Mice ; Mitochondria, Liver/drug effects ; Mitochondria, Liver/metabolism ; NAD/drug effects ; NAD/metabolism ; Nitric Oxide Synthase Type I/antagonists & inhibitors ; Oxidative Stress/drug effects ; Oxygen Consumption/drug effects ; Reactive Nitrogen Species/metabolism ; Reactive Oxygen Species/metabolism
Chemical Substances	Analgesics, Non-Narcotic ; Enzyme Inhibitors ; Guanidines ; N-(4-amino-5-((2-aminoethyl)amino)pentyl)-N'-nitroguanidine ; Reactive Nitrogen Species ; Reactive Oxygen Species ; NAD (0U46U6E8UK) ; Acetaminophen (362O9ITL9D) ; Nitric Oxide Synthase Type I (EC 1.14.13.39)
Language	English
Publishing date	2015-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2015.09.022
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Article: Trifluoperazine inhibits acetaminophen-induced hepatotoxicity and hepatic reactive nitrogen formation in mice and in freshly isolated hepatocytes

Banerjee, Sudip / Melnyk, Stepan B / Krager, Kimberly J / Aykin-Burns, Nukhet / McCullough, Sandra S / James, Laura P / Hinson, Jack A

Toxicology reports. 2017, v. 4

2017

Abstract	The hepatotoxicity of acetaminophen (APAP) occurs by initial metabolism to N-acetyl-p-benzoquinone imine which depletes GSH and forms APAP-protein adducts. Subsequently, the reactive nitrogen species peroxynitrite is formed from nitric oxide (NO) and superoxide leading to 3-nitrotyrosine in proteins. Toxicity occurs with inhibited mitochondrial function. We previously reported that in hepatocytes the nNOS (NOS1) inhibitor NANT inhibited APAP toxicity, reactive nitrogen and oxygen species formation, and mitochondrial dysfunction. In this work we examined the effect of trifluoperazine (TFP), a calmodulin antagonist that inhibits calcium induced nNOS activation, on APAP hepatotoxicity and reactive nitrogen formation in murine hepatocytes and in vivo. In freshly isolated hepatocytes TFP inhibited APAP induced toxicity, reactive nitrogen formation (NO, GSNO, and 3-nitrotyrosine in protein), reactive oxygen formation (superoxide), loss of mitochondrial membrane potential, decreased ATP production, decreased oxygen consumption rate, and increased NADH accumulation. TFP did not alter APAP induced GSH depletion in the hepatocytes or the formation of APAP protein adducts which indicated that reactive metabolite formation was not inhibited. Since we previously reported that TFP inhibits the hepatotoxicity of APAP in mice without altering hepatic APAP-protein adduct formation, we examined the APAP treated mouse livers for evidence of reactive nitrogen formation. 3-Nitrotyrosine in hepatic proteins and GSNO were significantly increased in APAP treated mouse livers and decreased in the livers of mice treated with APAP plus TFP. These data are consistent with a hypothesis that APAP hepatotoxicity occurs with altered calcium metabolism, activation of nNOS leading to increased reactive nitrogen formation, and mitochondrial dysfunction.
Keywords	acetaminophen ; antagonists ; calcium ; calmodulin ; hepatocytes ; hepatotoxicity ; imines ; membrane potential ; metabolism ; metabolites ; mice ; mitochondria ; mitochondrial membrane ; nitric oxide ; nitrogen ; oxygen ; oxygen consumption ; reactive nitrogen species ; toxicology ; trifluoperazine
Language	English
Size	p. 134-142.
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2805786-7
ISSN	2214-7500
ISSN	2214-7500
DOI	10.1016/j.toxrep.2017.02.005
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Article: Chlorotyrosine protein adducts are reliable biomarkers of neutrophil-induced cytotoxicity in vivo.

Gujral, Jaspreet S / Hinson, Jack A / Jaeschke, Hartmut

Comparative hepatology

2004 Volume 3 Suppl 1, Page(s) S48

Abstract: INTRODUCTION: A limitation for investigating the pathophysiological role of neutrophils in vivo is the lack of a reliable biomarker for neutrophil cytotoxicity in the liver. Therefore, we investigated if immunohistochemical detection of chlorotyrosine ... ...

Abstract	INTRODUCTION: A limitation for investigating the pathophysiological role of neutrophils in vivo is the lack of a reliable biomarker for neutrophil cytotoxicity in the liver. Therefore, we investigated if immunohistochemical detection of chlorotyrosine protein adducts can be used as a specific footprint for generation of neutrophil-derived hypochlorous acid in vivo. METHODS: C3Heb/FeJ mice were treated with 100 micrograms/kg endotoxin (ET) alone or in combination with 700 mg/kg galactosamine (Gal/ET). Some animals received additionally two doses of 10 mg/kg of the pancaspase inhibitor Z-VAD-fmk. An antibody against chlorotyrosine was used for the immunohistochemical analysis. RESULTS: At 6 h after Gal/ET, hepatocellular apoptosis was evident without increase in plasma ALT activities. Neutrophils accumulated in sinusoids but there was no evidence for chlorotyrosine staining. At 7 h after Gal/ET, about 54% of the sequestered neutrophils had extravasated, there was extensive necrosis and increased plasma ALT activities. Extensive immunostaining for chlorotyrosine, mainly colocalized with neutrophils, could be observed. Treatment with Z-VAD-fmk eliminated apoptosis, necrosis and the increase in plasma ALT values. Neutrophil extravasation was prevented but the overall number of neutrophils in the liver was unchanged. Chlorotyrosine staining was absent in these samples. After ET alone (7 h), sinusoidal neutrophil accumulation was similar to Gal/ET treatment but there was no apoptosis, neutrophil extravasation, ALT release or chlorotyrosine staining. CONCLUSIONS: Chlorotyrosine staining in liver samples correlated well with evidence of neutrophil-induced liver injury in the endotoxemia model. These results indicate that assessment of chlorotyrosine protein adduct formation by immunohistochemistry could be a useful marker of neutrophil-induced liver cell injury in vivo.
Language	English
Publishing date	2004-01-14
Publishing country	England
Document type	Journal Article
ISSN	1476-5926
ISSN	1476-5926
DOI	10.1186/1476-5926-2-S1-S48
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