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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

Effects of body temperature (BT) care in mice after saline injection. A. Survival curves in mice with and without BT care. B. Changes of BT in mice with and without BT care. C. Biochemical parameters and coagulation profile in mice with or without BT care. D. Histopathological findings in mice with BT care (hematoxylin-eosin, ×100). Normal findings were confirmed in mice with BT care.ALT, alanine aminotransferase; AST, aspartate aminotransferase; NS, not significant; PT-INR, international normalized ratio of prothrombin time; T-Bil, total bilirubin
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Figure 2: Effects of body temperature (BT) care in mice after saline injection. A. Survival curves in mice with and without BT care. B. Changes of BT in mice with and without BT care. C. Biochemical parameters and coagulation profile in mice with or without BT care. D. Histopathological findings in mice with BT care (hematoxylin-eosin, ×100). Normal findings were confirmed in mice with BT care.ALT, alanine aminotransferase; AST, aspartate aminotransferase; NS, not significant; PT-INR, international normalized ratio of prothrombin time; T-Bil, total bilirubin

Mentions: First, the effect of BT care itself was investigated in mice receiving saline injections. There were two groups of mice: those who were given BT care after saline injections (0.50 mL/ mouse, i.p.; n = 10), and mice who received no such care after saline injections (n = 10). Hydration supplements were given every 6 h after saline injections. Survival and BT were checked every 2 h. Liver and blood samples were taken 30 h after initial injections. There were no significant differences between the two control groups in survival curves (Fig. 2A), changes in BT over time (Fig. 2B), or levels of AST, ALT, T-Bil and PTINR (Fig. 2C) (P ≥ 0.05 for all categories). Histopathological assessment showed normal findings in mice with BT care (Fig. 2D). Hence, BT care had no effects on control mice.


Fulminant liver failure model with hepatic encephalopathy in the mouse.

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

Effects of body temperature (BT) care in mice after saline injection. A. Survival curves in mice with and without BT care. B. Changes of BT in mice with and without BT care. C. Biochemical parameters and coagulation profile in mice with or without BT care. D. Histopathological findings in mice with BT care (hematoxylin-eosin, ×100). Normal findings were confirmed in mice with BT care.ALT, alanine aminotransferase; AST, aspartate aminotransferase; NS, not significant; PT-INR, international normalized ratio of prothrombin time; T-Bil, total bilirubin
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Effects of body temperature (BT) care in mice after saline injection. A. Survival curves in mice with and without BT care. B. Changes of BT in mice with and without BT care. C. Biochemical parameters and coagulation profile in mice with or without BT care. D. Histopathological findings in mice with BT care (hematoxylin-eosin, ×100). Normal findings were confirmed in mice with BT care.ALT, alanine aminotransferase; AST, aspartate aminotransferase; NS, not significant; PT-INR, international normalized ratio of prothrombin time; T-Bil, total bilirubin
Mentions: First, the effect of BT care itself was investigated in mice receiving saline injections. There were two groups of mice: those who were given BT care after saline injections (0.50 mL/ mouse, i.p.; n = 10), and mice who received no such care after saline injections (n = 10). Hydration supplements were given every 6 h after saline injections. Survival and BT were checked every 2 h. Liver and blood samples were taken 30 h after initial injections. There were no significant differences between the two control groups in survival curves (Fig. 2A), changes in BT over time (Fig. 2B), or levels of AST, ALT, T-Bil and PTINR (Fig. 2C) (P ≥ 0.05 for all categories). Histopathological assessment showed normal findings in mice with BT care (Fig. 2D). Hence, BT care had no effects on control mice.

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