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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

Histopathological findings for liver-related deaths in both fulminant liver failure (FLF) models with body temperature (BT) care. Consistent findings of FLF, such as massive necrosis, intrahepatic bleeding, vacuolization and inflammatory cells infiltrations, were confirmed. A. Histopathological findings in mice treated with azoxymethane (AOM) with BT care (hematoxylin-eosin, ×100). B. Histopathological findings in mice treated with AOM with BT care (hematoxylin-eosin, ×200). C. Histopathological findings in mice treated with galactosamine (Gal) + tumor necrosis factor (TNF)α with BT care (hematoxylin-eosin, ×100). D. Histopathological findings in mice treated with Gal+TNFα with BT care (hematoxylin-eosin, ×200).
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Figure 4: Histopathological findings for liver-related deaths in both fulminant liver failure (FLF) models with body temperature (BT) care. Consistent findings of FLF, such as massive necrosis, intrahepatic bleeding, vacuolization and inflammatory cells infiltrations, were confirmed. A. Histopathological findings in mice treated with azoxymethane (AOM) with BT care (hematoxylin-eosin, ×100). B. Histopathological findings in mice treated with AOM with BT care (hematoxylin-eosin, ×200). C. Histopathological findings in mice treated with galactosamine (Gal) + tumor necrosis factor (TNF)α with BT care (hematoxylin-eosin, ×100). D. Histopathological findings in mice treated with Gal+TNFα with BT care (hematoxylin-eosin, ×200).

Mentions: Histopathological findings of liver-related deaths in both FLF models are shown in Fig. 4 (H-E, ×100 and ×200). In both FLF models given BT care, histopathological assessment showed consistent FLF findings, such as massive necrosis, intrahepatic bleeding, vacuolization and inflammatory cells infiltrations. Levels of AST, ALT, T-Bil and PT-INR are shown in Fig. 5. While there were no significant differences in ALT (949.1 ± 77.7 vs. 814.1±200.3 U/L, P ≥ 0.05) and T-Bil (1.68±0.55 vs. 1.31±0.28 mg/dL, P ≥ 0.05) between the FLF models, there were significant differences in AST (896.1±108.8 vs. 727.2±219.7 U/L, P = 0.0429) and PT-INR (0.77±0.05 vs. 0.87±0.09, P = 0.0135).


Fulminant liver failure model with hepatic encephalopathy in the mouse.

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

Histopathological findings for liver-related deaths in both fulminant liver failure (FLF) models with body temperature (BT) care. Consistent findings of FLF, such as massive necrosis, intrahepatic bleeding, vacuolization and inflammatory cells infiltrations, were confirmed. A. Histopathological findings in mice treated with azoxymethane (AOM) with BT care (hematoxylin-eosin, ×100). B. Histopathological findings in mice treated with AOM with BT care (hematoxylin-eosin, ×200). C. Histopathological findings in mice treated with galactosamine (Gal) + tumor necrosis factor (TNF)α with BT care (hematoxylin-eosin, ×100). D. Histopathological findings in mice treated with Gal+TNFα with BT care (hematoxylin-eosin, ×200).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Histopathological findings for liver-related deaths in both fulminant liver failure (FLF) models with body temperature (BT) care. Consistent findings of FLF, such as massive necrosis, intrahepatic bleeding, vacuolization and inflammatory cells infiltrations, were confirmed. A. Histopathological findings in mice treated with azoxymethane (AOM) with BT care (hematoxylin-eosin, ×100). B. Histopathological findings in mice treated with AOM with BT care (hematoxylin-eosin, ×200). C. Histopathological findings in mice treated with galactosamine (Gal) + tumor necrosis factor (TNF)α with BT care (hematoxylin-eosin, ×100). D. Histopathological findings in mice treated with Gal+TNFα with BT care (hematoxylin-eosin, ×200).
Mentions: Histopathological findings of liver-related deaths in both FLF models are shown in Fig. 4 (H-E, ×100 and ×200). In both FLF models given BT care, histopathological assessment showed consistent FLF findings, such as massive necrosis, intrahepatic bleeding, vacuolization and inflammatory cells infiltrations. Levels of AST, ALT, T-Bil and PT-INR are shown in Fig. 5. While there were no significant differences in ALT (949.1 ± 77.7 vs. 814.1±200.3 U/L, P ≥ 0.05) and T-Bil (1.68±0.55 vs. 1.31±0.28 mg/dL, P ≥ 0.05) between the FLF models, there were significant differences in AST (896.1±108.8 vs. 727.2±219.7 U/L, P = 0.0429) and PT-INR (0.77±0.05 vs. 0.87±0.09, P = 0.0135).

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