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Fulminant liver failure model with hepatic encephalopathy in the mouse.

Hori T, Chen F, Baine AM, Gardner LB, Nguyen JH - Ann Gastroenterol (2011)

Bottom Line: The AOM group, but not the Gal+TNFα group, showed significant differences in survival curves between those with and without 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.Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Mayo Clinic in Florida, Jacksonville, FL 32224, USA (Tomohide Hori, Feng Chen, Ann-Marie T. Baine, Lindsay B. Gardner).

ABSTRACT

Aim: To develop a reliable murine model for fulminant liver failure (FLF).

Material and 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Dose-dependent survival curves after galactosamine (Gal) + tumor necrosis factor (TNF)αinjections, with body temperature (BT) care.
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Figure 7: Dose-dependent survival curves after galactosamine (Gal) + tumor necrosis factor (TNF)αinjections, with body temperature (BT) care.

Mentions: For TNFα, researchers have used doses ranging from 0.001 to 0.1 µg/g bw [15,30-34]. We used TNFα doses of 0.01, 0.02, 0.05, 0.10, 0.20, 0.50 and 1.00 µg/g bw, (n = 10 for each dose) because all mice receiving TNFα ≤ 0.02 µg/g bw in the preliminary study survived. Survival curves for mice after Gal+TNFα injections with BT care are shown in Fig. 7.


Fulminant liver failure model with hepatic encephalopathy in the mouse.

Hori T, Chen F, Baine AM, Gardner LB, Nguyen JH - Ann Gastroenterol (2011)

Dose-dependent survival curves after galactosamine (Gal) + tumor necrosis factor (TNF)αinjections, with body temperature (BT) care.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3959336&req=5

Figure 7: Dose-dependent survival curves after galactosamine (Gal) + tumor necrosis factor (TNF)αinjections, with body temperature (BT) care.
Mentions: For TNFα, researchers have used doses ranging from 0.001 to 0.1 µg/g bw [15,30-34]. We used TNFα doses of 0.01, 0.02, 0.05, 0.10, 0.20, 0.50 and 1.00 µg/g bw, (n = 10 for each dose) because all mice receiving TNFα ≤ 0.02 µg/g bw in the preliminary study survived. Survival curves for mice after Gal+TNFα injections with BT care are shown in Fig. 7.

Bottom Line: The AOM group, but not the Gal+TNFα group, showed significant differences in survival curves between those with and without 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.Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Mayo Clinic in Florida, Jacksonville, FL 32224, USA (Tomohide Hori, Feng Chen, Ann-Marie T. Baine, Lindsay B. Gardner).

ABSTRACT

Aim: To develop a reliable murine model for fulminant liver failure (FLF).

Material and 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus