Table 3.
Effect of Long-Term Ligand Activation of PPARα With GW7647 Initiated in Perinatal Development on Liver Histopathology (and Overtly Present Liver Lesions) in Wild-Type (Ppara+/+), Ppara-Null (Ppara–/–), or PPARA Humanized Mice (PPARA)
|
Ppara
+/+
|
Ppara
–/–
|
PPARA
|
|||||
|---|---|---|---|---|---|---|---|
| Control | GW7647 | Control | GW7647 | Control | GW7647 | ||
| Centrilobular hypertrophy | None | 6/13 | 6/7 | 6/11 | 12/13 | 14/17 | 0/14 |
| Mild | 6/13 | 1/7 | 5/11 | 1/13 | 3/17 | 8/14 | |
| Moderate | 1/13 | 0/7 | 0/11 | 0/13 | 0/17 | 5/14 | |
| Severe | 0/13 | 0/7 | 0/11 | 0/13 | 0/17 | 1/14 | |
| Necrosis | None | 13/13 | 5/7 | 10/11 | 12/13 | 16/17 | 13/14 |
| Present | 0/13 | 2/7 | 1/11 | 1/13 | 1/17 | 1/14 | |
| Inflammation | None | 5/13 | 0/7 | 4/11 | 4/13 | 6/17 | 3/14 |
| Acute | 0/13 | 0/7 | 0/11 | 0/13 | 0/17 | 0/14 | |
| Chronic | 8/13 | 7/7 | 7/11 | 9/13 | 11/17 | 11/14 | |
| Macrovesicular fatty change | None | 13/13 | 3/7 | 7/11 | 4/13 | 5/17 | 8/14 |
| Mild | 0/13 | 3/7 | 4/11 | 6/13 | 5/17 | 3/14 | |
| Moderate | 0/13 | 1/7 | 0/11 | 3/13 | 7/17 | 3/14 | |
| Severe | 0/13 | 0/7 | 0/11 | 0/13 | 0/17 | 0/14 | |
| Tumora | Total | 1/13 | 6/7 | 1/11 | 1/13 | 1/17 | 4/14 |
| Hepatocellular adenoma | 1/13 | 5/7 | 1/11 | 1/13 | 1/17 | 4/14 | |
| Hepatocellular carcinoma | 0/13 | 1/7 | 0/11 | 0/13 | 0/17 | 1/14 | |
| Gross findingsb | Tumor-like | 0/15 | 14/14 | 2/13 | 4/17 | 3/16 | 5/14 |
| Morbidity/Mortalityc | 1/16 | 7/14 | 2/15 | 0/17 | 1/17 | 2/16 | |
a
The number of tumors per slide identified histopathologically per group.
b
The number of mice with gross findings in the liver at the time of necropsy.
c
Mice that died or were euthanized for health reasons.