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

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.