Plasma alpha-glutathione S-transferase: a sensitive indicator of hepatocellular damage during polymicrobial sepsis.
OBJECTIVE
Since studies have found the liver enzyme alpha-glutathione S-transferase (alphaGST) to be a marker of hepatic injury after hemorrhagic shock, alphaGST also may serve as a sensitive indicator of hepatocellular damage during the early stage of polymicrobial sepsis.


METHODS
Male adult rats were subjected to the cecal ligation and puncture (CLP) model of polymicrobial sepsis or sham operation, followed by fluid resuscitation with isotonic sodium chloride solution. Systemic blood samples were taken at 2, 5, 10, or 20 hours after CLP or sham operation. Plasma levels of alphaGST and lactate were determined using an enzyme immunoassay and enzymatic assay, respectively. Additional animals were examined for morphologic alterations in liver ultrastructure of septic animals using electron microscopy.


RESULTS
A similar level of alphaGST (mean +/- SEM, 30.5 +/- 3.5 microg/L) was found in the sham group at all measured time points. Although plasma levels of alphaGST did not change at 2 hours after CLP, they were elevated by 249% at 5 hours after the onset of sepsis and continued to increase throughout the septic course. Plasma lactate levels were significantly increased only at 20 hours after CLP (P<.001). Previous studies have shown that liver transaminase levels did not increase at 5 hours, but at 10 and 20 hours after CLP. In addition, electron microscopy revealed structural changes in hepatocyte morphology at 5 and 20 hours after CLP that were indicative of hepatocellular injury.


CONCLUSIONS
Since plasma alphaGST levels increased earlier than plasma lactate and liver transaminase levels, alphaGST may be a more sensitive indicator of early liver injury and should be used in monitoring hepatocellular damage during the progression of sepsis.
Koo
D J
DJ
Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence 02903, USA.
Zhou
M
M
Chaudry
I H
IH
Wang
P
P
D000818:Animals; D015415:Biomarkers; D004796:Clinical Enzyme Tests; D005982:Glutathione Transferase / Q000097:blood*; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000648:ultrastructure*; D008111:Liver Function Tests; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000175:diagnosis*
D015415:Biomarkers; D019344:Lactic Acid; D005982:Glutathione Transferase