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Biomarkers Volume 19, 2014 - Issue 3
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Research Article

Argininosuccinate synthetase as a plasma biomarker of liver injury after acetaminophen overdose in rodents and humans

Mitchell R. McGillDepartment of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center Kansas City, KSUSA
,
Mengde CaoDepartment of Medicine, University of Florida Gainesville, FLUSA;Banyan Laboratories, Inc. Alachua, FLUSA
,
Archie SvetlovBanyan Laboratories, Inc. Alachua, FLUSA
,
Matthew R. SharpeDepartment of Internal Medicine, University of Kansas Hospital Kansas City, KSUSA
,
C. David WilliamsDepartment of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center Kansas City, KSUSA
,
Steven C. CurryDepartment of Medical Toxicology, Banner Good Samaritan Medical Center Phoenix, AZUSA;Department of Medicine, and Center for Toxicology and Pharmacology Education and Research, University of Arizona College of Medicine Phoenix, AZUSA
,
Anwar FarhoodDepartment of Pathology, St. David’s North Austin Medical Center Austin, TXUSA
,
Hartmut JaeschkeDepartment of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center Kansas City, KSUSACorrespondence[email protected]
[email protected]
&
Stanislav I. SvetlovDepartment of Medicine, University of Florida Gainesville, FLUSA;Banyan Laboratories, Inc. Alachua, FLUSACorrespondence[email protected]
 show all
Pages 222-230 | Received 10 Oct 2013, Accepted 20 Feb 2014, Published online: 06 Mar 2014
 
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Abstract

Context: New biomarkers are needed in acetaminophen (APAP) hepatotoxicity. Plasma argininosuccinate synthetase (ASS) is a promising candidate.

Objective: Characterize ASS in APAP hepatotoxicity.

Methods: ASS was measured in plasma from rodents and humans with APAP hepatotoxicity.

Results: In mice, ASS increased before injury, peaked before alanine aminotransferase (ALT) and decreased rapidly. Fischer rats had a greater increase in ASS relative to ALT. Patients with abnormal liver test results had very high ASS compared to controls. ASS appeared to increase early in some patients, and declined rapidly in all.

Conclusions: ASS may be a useful biomarker of acute cell death in APAP hepatotoxicity.

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