Fulminant liver failure model with hepatic encephalopathy in the mouse.
OBJECTIVE
To develop a reliable murine model for fulminant liver failure (FLF).


METHODS
We treated three groups of male C57BL/6 mice:as controls, with azoxymethane (AOM), and with galactosamine (Gal) and tumor necrosis factor-alpha (TNFα). Effects of body temperature (BT) control on survival, in all three groups were investigated. Using BT control, survival, histopathological findings and biochemical/coagulation profiles were compared between the experimental groups. Effects of hydration on international normalized ratios of prothrombin time (PT-INR) were also checked. Dose-dependent survival curves were made for both experimental groups. Neurological behaviors were assessed using a coma scale.


RESULTS
No unexpected BT effects were seen in the control group. The AOM group, but not the Gal+TNFα group, showed significant differences in survival curves between those with and without BT care. Histopathological assessment showed consistent FLF findings in both experimental groups with BT care. Between the experimental groups, there were significant differences in aspartate aminotransferase levels and PT-INR; and significant differences in PT-INRs between sufficiently- and insufficiently-hydrated groups. There were significant differences between FLF models, in the duration of each coma stage, with significant differences in stages 1 and 3 as percentages of the diseased state (stages 1-4). The two FLF models with BT care showed different survival curves in the dose-dependent survival study.


CONCLUSIONS
Azoxymethane can provide a good FLF model, but requires a specialized environment and careful BT control. Other FLF models may also be useful, depending on research purpose. Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.
Department of Neuroscience, Mayo Clinic in Florida, Jacksonville, FL 32224, USA (Tomohide Hori, Feng Chen, Ann-Marie T. Baine, Lindsay B. Gardner).
Tomohide
T
Hori
Department of Neuroscience, Mayo Clinic in Florida, Jacksonville, FL 32224, USA (Tomohide Hori, Feng Chen, Ann-Marie T. Baine, Lindsay B. Gardner).
Feng
F
Chen
Department of Neuroscience, Mayo Clinic in Florida, Jacksonville, FL 32224, USA (Tomohide Hori, Feng Chen, Ann-Marie T. Baine, Lindsay B. Gardner).
Ann-Marie T
AM
Baine
Department of Neuroscience, Mayo Clinic in Florida, Jacksonville, FL 32224, USA (Tomohide Hori, Feng Chen, Ann-Marie T. Baine, Lindsay B. Gardner).
Lindsay B
LB
Gardner
Department of Neuroscience, Mayo Clinic in Florida, Jacksonville, FL 32224, USA (Tomohide Hori, Feng Chen, Ann-Marie T. Baine, Lindsay B. Gardner).
Justin H
JH
Nguyen
Animal model; acute liver failure; azoxymethane; galactosamine; tumor necrosis factor-alpha