Detection of ophthalmic acid in serum from acetaminophen-induced acute liver failure patients is more frequent in non-survivors

Gurnit Kaur, Elaine M. Leslie, Holly Tillman, William M. Lee, Diane P. Swanlund, Constantine J. Karvellas, Anne M. Larson, Iris Liou, Oren Fix, Michael Schilsky, Daniel Ganger, Steven H B Han, Robert Fontana, Brendan McGuire, Adrian Reuben, David Koch, Rajender Reddy, R. Todd Stravitz, James Hanje, Jody Olson & 13 others Ram Subramanian, Grace Samuel, Ezmina Lalani, Carla Pezzia, Corron Sanders, Nahid Attar, Linda S. Hynan, Valerie Durkalski, Wenle Zhao, Jaime Speiser, Catherine Dillon, Holly Battenhouse, Michelle Gottfried

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background/Aim: Acetaminophen (APAP) hepatotoxicity is related to the formation of N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified through conjugation with reduced glutathione (GSH). Ophthalmic acid (OA) is an analogue of GSH in which cysteine is replaced with 2-aminobutyrate. Metabolomics studies of mice with APAP-induced acute liver failure (APAPALF) identified OA as a marker of oxidative stress and hepatic GSH consumption. The aim of the current study was to determine whether OA is detectable in APAP-ALF human patients either early (day 2) or late (day 4) and whether OA levels were associated with inhospital survival in the absence of liver transplant. Methods: Serum samples from 130 APAP-ALF patients (82 survivors, 48 non-survivors) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and correlated with clinical data from the United States Acute Liver Failure Study Group (US ALFSG) Registry (2004-2011). Results: Survivors had significantly lower admission bilirubin (4.2 vs. 5.7 mg/dl) and lactate levels (3.3 vs. 6.5 μmol/l, p 0.5 for all). Conclusion: OA was detectable more frequently in APAP-ALF non-survivors but mean OA levels were not associated with survival. The routine clinical administration of N-acetyl cysteine could replenish GSH levels and prevent OA production.

Original languageEnglish (US)
Article numbere0139299
JournalPLoS One
Volume10
Issue number9
DOIs
StatePublished - Sep 25 2015

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acetaminophen
liver failure
Acute Liver Failure
Acetaminophen
Liver
eyes
acids
Serum
Cysteine
Survivors
Acetylcysteine
Aminobutyrates
liver transplant
benzoquinones
Transplants
acetylcysteine
Oxidative stress
Imines
Metabolomics
Survival

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Detection of ophthalmic acid in serum from acetaminophen-induced acute liver failure patients is more frequent in non-survivors. / Kaur, Gurnit; Leslie, Elaine M.; Tillman, Holly; Lee, William M.; Swanlund, Diane P.; Karvellas, Constantine J.; Larson, Anne M.; Liou, Iris; Fix, Oren; Schilsky, Michael; Ganger, Daniel; Han, Steven H B; Fontana, Robert; McGuire, Brendan; Reuben, Adrian; Koch, David; Reddy, Rajender; Stravitz, R. Todd; Hanje, James; Olson, Jody; Subramanian, Ram; Samuel, Grace; Lalani, Ezmina; Pezzia, Carla; Sanders, Corron; Attar, Nahid; Hynan, Linda S.; Durkalski, Valerie; Zhao, Wenle; Speiser, Jaime; Dillon, Catherine; Battenhouse, Holly; Gottfried, Michelle.

In: PLoS One, Vol. 10, No. 9, e0139299, 25.09.2015.

Research output: Contribution to journalArticle

Kaur, G, Leslie, EM, Tillman, H, Lee, WM, Swanlund, DP, Karvellas, CJ, Larson, AM, Liou, I, Fix, O, Schilsky, M, Ganger, D, Han, SHB, Fontana, R, McGuire, B, Reuben, A, Koch, D, Reddy, R, Stravitz, RT, Hanje, J, Olson, J, Subramanian, R, Samuel, G, Lalani, E, Pezzia, C, Sanders, C, Attar, N, Hynan, LS, Durkalski, V, Zhao, W, Speiser, J, Dillon, C, Battenhouse, H & Gottfried, M 2015, 'Detection of ophthalmic acid in serum from acetaminophen-induced acute liver failure patients is more frequent in non-survivors', PLoS One, vol. 10, no. 9, e0139299. https://doi.org/10.1371/journal.pone.0139299
Kaur, Gurnit ; Leslie, Elaine M. ; Tillman, Holly ; Lee, William M. ; Swanlund, Diane P. ; Karvellas, Constantine J. ; Larson, Anne M. ; Liou, Iris ; Fix, Oren ; Schilsky, Michael ; Ganger, Daniel ; Han, Steven H B ; Fontana, Robert ; McGuire, Brendan ; Reuben, Adrian ; Koch, David ; Reddy, Rajender ; Stravitz, R. Todd ; Hanje, James ; Olson, Jody ; Subramanian, Ram ; Samuel, Grace ; Lalani, Ezmina ; Pezzia, Carla ; Sanders, Corron ; Attar, Nahid ; Hynan, Linda S. ; Durkalski, Valerie ; Zhao, Wenle ; Speiser, Jaime ; Dillon, Catherine ; Battenhouse, Holly ; Gottfried, Michelle. / Detection of ophthalmic acid in serum from acetaminophen-induced acute liver failure patients is more frequent in non-survivors. In: PLoS One. 2015 ; Vol. 10, No. 9.
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abstract = "Background/Aim: Acetaminophen (APAP) hepatotoxicity is related to the formation of N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified through conjugation with reduced glutathione (GSH). Ophthalmic acid (OA) is an analogue of GSH in which cysteine is replaced with 2-aminobutyrate. Metabolomics studies of mice with APAP-induced acute liver failure (APAPALF) identified OA as a marker of oxidative stress and hepatic GSH consumption. The aim of the current study was to determine whether OA is detectable in APAP-ALF human patients either early (day 2) or late (day 4) and whether OA levels were associated with inhospital survival in the absence of liver transplant. Methods: Serum samples from 130 APAP-ALF patients (82 survivors, 48 non-survivors) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and correlated with clinical data from the United States Acute Liver Failure Study Group (US ALFSG) Registry (2004-2011). Results: Survivors had significantly lower admission bilirubin (4.2 vs. 5.7 mg/dl) and lactate levels (3.3 vs. 6.5 μmol/l, p 0.5 for all). Conclusion: OA was detectable more frequently in APAP-ALF non-survivors but mean OA levels were not associated with survival. The routine clinical administration of N-acetyl cysteine could replenish GSH levels and prevent OA production.",
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T1 - Detection of ophthalmic acid in serum from acetaminophen-induced acute liver failure patients is more frequent in non-survivors

AU - Kaur, Gurnit

AU - Leslie, Elaine M.

AU - Tillman, Holly

AU - Lee, William M.

AU - Swanlund, Diane P.

AU - Karvellas, Constantine J.

AU - Larson, Anne M.

AU - Liou, Iris

AU - Fix, Oren

AU - Schilsky, Michael

AU - Ganger, Daniel

AU - Han, Steven H B

AU - Fontana, Robert

AU - McGuire, Brendan

AU - Reuben, Adrian

AU - Koch, David

AU - Reddy, Rajender

AU - Stravitz, R. Todd

AU - Hanje, James

AU - Olson, Jody

AU - Subramanian, Ram

AU - Samuel, Grace

AU - Lalani, Ezmina

AU - Pezzia, Carla

AU - Sanders, Corron

AU - Attar, Nahid

AU - Hynan, Linda S.

AU - Durkalski, Valerie

AU - Zhao, Wenle

AU - Speiser, Jaime

AU - Dillon, Catherine

AU - Battenhouse, Holly

AU - Gottfried, Michelle

PY - 2015/9/25

Y1 - 2015/9/25

N2 - Background/Aim: Acetaminophen (APAP) hepatotoxicity is related to the formation of N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified through conjugation with reduced glutathione (GSH). Ophthalmic acid (OA) is an analogue of GSH in which cysteine is replaced with 2-aminobutyrate. Metabolomics studies of mice with APAP-induced acute liver failure (APAPALF) identified OA as a marker of oxidative stress and hepatic GSH consumption. The aim of the current study was to determine whether OA is detectable in APAP-ALF human patients either early (day 2) or late (day 4) and whether OA levels were associated with inhospital survival in the absence of liver transplant. Methods: Serum samples from 130 APAP-ALF patients (82 survivors, 48 non-survivors) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and correlated with clinical data from the United States Acute Liver Failure Study Group (US ALFSG) Registry (2004-2011). Results: Survivors had significantly lower admission bilirubin (4.2 vs. 5.7 mg/dl) and lactate levels (3.3 vs. 6.5 μmol/l, p 0.5 for all). Conclusion: OA was detectable more frequently in APAP-ALF non-survivors but mean OA levels were not associated with survival. The routine clinical administration of N-acetyl cysteine could replenish GSH levels and prevent OA production.

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