TABLE 3.
Effect of DE-71 on Hepatic UGT-T4 Protein Activity and Gene Expression
Target | Treatment (mg/kg/day) | PND 4 | PND 21 | PND 60 |
UGT-T4a | 0 | 0.6 ± 0.1 | 0.6 ± 0.1 | 0.5 ± 0.1 |
1.7 | 0.6 ± 0.1 | 0.6 ± 0.1 | 0.5 ± 0.0 | |
10.2 | 0.7 ± 0.1 | 0.7 ± 0.2 | 0.5 ± 0.1 | |
30.6 | 1.5 ± 0.3** | 1.7 ± 0.4** | 0.5 ± 0.1 | |
Ugt1a1b | 0 | 1.2 ± 0.4 | 0.2 ± 0.1 | 0.1 ± 0.1 |
1.7 | 1.7 ± 0.5 | 0.2 ± 0.1 | 0.1 ± 0.0 | |
10.2 | 1.7 ± 0.4 | 0.2 ± 0.0 | 0.1 ± 0.0 | |
30.6 | 1.5 ± 0.2 | 0.1 ± 0.0 | 0.1 ± 0.0 | |
Ugt1a6b | 0 | 1.8 ± 1.0 | 229.4 ± 12.1 | 79.7 ± 16.0 |
1.7 | 3.4 ± 1.3 | 245.2 ± 34.2 | 98.3 ± 16.2 | |
10.2 | 12.8 ± 4.8** | 229.5 ± 17.8 | 108.7 ± 16.9 | |
30.6 | 34.0 ± 10.5* | 201.1 ± 30.2 | 112.1 ± 17.8 | |
Ugt1a7b | 0 | 1.8 ± 0.2 | 0.3 ± 0.1 | 0.003 ± 0.0003 |
1.7 | 2.5 ± 0.5 | 0.3 ± 0.1 | 0.003 ± 0.0005 | |
10.2 | 2.9 ± 0.8** | 0.4 ± 0.1 | 0.003 ± 0.0002 | |
30.6 | 3.8 ± 1.5** | 0.7 ± 0.2* | 0.004 ± 0.0005 | |
Ugt2bb | 0 | 1.2 ± 0.4 | 1.2 ± 0.7 | 7534 ± 2963 |
1.7 | 1.0 ± 0.4 | 7.6 ± 6.0 | 10,043 ± 3581 | |
10.2 | 1.3 ± 1.0 | 1.5 ± 0.3 | 9881 ± 2274 | |
30.6 | 6.5 ± 2.2* | 78.0 ± 9.3* | 11,318 ± 2227 |
Note. Phase II hepatic microsomal enzyme activity was measured for UGTs using T4 as a substrate along with real-time PCR of Ugt1a1, Ugt1a6, Ugt1a7, and Ugt2b gene expression. Microsomes and RNA were isolated from male rat livers at PND 4, 21, and 60 after perinatal exposure to the polybrominated diphenyl ether mixture, DE-71 (0, 1.7, 10.2, and 30.6 mg/kg/day) from GD 6 to PND 21. Significantly different from control: (p < 0.01)* or (p < 0.05)**.
Data are expressed as pmol/mg protein/min ± SD, n = 5.
Data are expressed as relative quantitation mean ± SD.