Fulminant liver failure models with subsequent encephalopathy in the mouse

A. M T Baine, Tomohide Hori, Feng Chen, Lindsay B. Gardner, Shinji Uemoto, Justin H Nguyen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A reliable model of fulminant liver failure (FLF) is urgently required in this research field. This study aimed to develop a murine FLF model. METHODS: We used three groups of male C57BL/6 mice: control, with azoxymethane treatment (AOM group), and with galactosamine and tumor necrosis factor alpha treatment (Gal+TNF-α group). The effects of body temperature (BT) control on survival in all three groups were investigated. Using BT control, we compared the survival, histopathological findings and biochemical/coagulation profiles between the two experimental groups. The effects of hydration on international normalized ratios of prothrombin time (PTINRs) were also checked. Dose-dependent survival curves were constructed for both experimental groups. Neurological behavior was assessed using a coma scale. RESULTS: No unexpected BT effects were seen in the control group. The AOM group, but not the Gal+TNF-α group, showed a significant difference in survival curves between those with and without BT care. Histopathological assessment showed consistent FLF findings in both experimental groups with BT care. There were significant differences between the experimental groups in aspartate aminotransferase levels and PT-INRs, and significant differences in PT-INRs between the 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 disease state (stages 1-4). The two FLF models with BT care showed different survival curves in the dose-dependent survival study. CONCLUSIONS: AOM provides a good FLF model, but requires a specialized environment and careful BT control. Other FLF models may also be useful, depending on the research purpose. Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.

Original languageEnglish (US)
Pages (from-to)611-619
Number of pages9
JournalHepatobiliary and Pancreatic Diseases International
Volume10
Issue number6
DOIs
StatePublished - Dec 2011

Fingerprint

Acute Liver Failure
Brain Diseases
Body Temperature
International Normalized Ratio
Coma
Azoxymethane
Galactosamine
Prothrombin Time
Aspartate Aminotransferases
Inbred C57BL Mouse
Research
Tumor Necrosis Factor-alpha
Observation
Control Groups

Keywords

  • Acute liver failure
  • Animal model
  • Azoxymethane
  • Galactosamine
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Fulminant liver failure models with subsequent encephalopathy in the mouse. / Baine, A. M T; Hori, Tomohide; Chen, Feng; Gardner, Lindsay B.; Uemoto, Shinji; Nguyen, Justin H.

In: Hepatobiliary and Pancreatic Diseases International, Vol. 10, No. 6, 12.2011, p. 611-619.

Research output: Contribution to journalArticle

Baine, A. M T ; Hori, Tomohide ; Chen, Feng ; Gardner, Lindsay B. ; Uemoto, Shinji ; Nguyen, Justin H. / Fulminant liver failure models with subsequent encephalopathy in the mouse. In: Hepatobiliary and Pancreatic Diseases International. 2011 ; Vol. 10, No. 6. pp. 611-619.
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abstract = "A reliable model of fulminant liver failure (FLF) is urgently required in this research field. This study aimed to develop a murine FLF model. METHODS: We used three groups of male C57BL/6 mice: control, with azoxymethane treatment (AOM group), and with galactosamine and tumor necrosis factor alpha treatment (Gal+TNF-α group). The effects of body temperature (BT) control on survival in all three groups were investigated. Using BT control, we compared the survival, histopathological findings and biochemical/coagulation profiles between the two experimental groups. The effects of hydration on international normalized ratios of prothrombin time (PTINRs) were also checked. Dose-dependent survival curves were constructed for both experimental groups. Neurological behavior was assessed using a coma scale. RESULTS: No unexpected BT effects were seen in the control group. The AOM group, but not the Gal+TNF-α group, showed a significant difference in survival curves between those with and without BT care. Histopathological assessment showed consistent FLF findings in both experimental groups with BT care. There were significant differences between the experimental groups in aspartate aminotransferase levels and PT-INRs, and significant differences in PT-INRs between the 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 disease state (stages 1-4). The two FLF models with BT care showed different survival curves in the dose-dependent survival study. CONCLUSIONS: AOM provides a good FLF model, but requires a specialized environment and careful BT control. Other FLF models may also be useful, depending on the research purpose. Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.",
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