TABLE 4.
Changes in mRNA Expression of a Panel of Novel Renal Biomarkers in Kidneys of Male Wistar Rats Repeatedly Dosed with BI-2, BI-3, Gentamicin, or IMM125 for 1, 3, or 14 Days
| Days of treatment | BI-2 fold change (relative to control) |
BI-3 fold change (relative to control) |
Gentamicin fold change (relative to control) |
IMM125 fold change (relative to control) |
|||||||||
| Gene | 0 mg/kg | 2.5 mg/kg | 15 mg/kg | 0 mg/kg | 100 mg/kg | 1000 mg/kg | 0 mg/kg | 25 mg/kg | 75 mg/kg | 0 mg/kg | 30 mg/kg | 100 mg/kg | |
| Kim-1 (hepatitis A virus cellular receptor 1) | 1 | 1.0 ± 0.2 | 0.8 ± 0.4 | 0.9 ± 0.4 | 1.0 ± 0.5 | 1.1 ± 0.8 | 0.9 ± 0.6 | 1.0 ± 0.5 | 0.9 ± 0.2 | 0.9 ± 0.3 | 1.0 ± 0.2 | 2.5 ± 1.3 | 3.4 ± 2.1* |
| 3 | 1.0 ± 0.4 | 1.0 ± 0.3 | 0.9 ± 0.3 | 1.0 ± 0.4 | 0.9 ± 0.2 | 11.2 ± 23.5 | 1.0 ± 0.3 | 1.1 ± 0.3 | 2.1 ± 1.2 | 1.0 ± 0.3 | 2.9 ± 3.5 | 9.9 ± 6.0** | |
| 14 | 1.0 ± 0.3 | 0.8 ± 0.3 | 0.7 ± 0.1 | 1.0 ± 0.5 | 0.5 ± 0.2 | 392.5 ± 450.5 | 1.0 ± 0.2 | 91.2 ± 92.0 | 191.7 ± 100.8** | 1.0 ± 0.3 | 3.1 ± 2.1 | 51.6 ± 29.9** | |
| Clusterin | 1 | 1.0 ± 0.1 | 1.0 ± 0.1 | 0.9 ± 0.1 | 1.0 ± 0.4 | 1.1 ± 0.5 | 1.0 ± 0.4 | 1.0 ± 0.2 | 1.1 ± 0.2 | 1.0 ± 0.1 | 1.0 ± 0.3 | 0.7 ± 0.3 | 0.6 ± 0.3 |
| 3 | 1.0 ± 0.1 | 1.0 ± 0.1 | 0.9 ± 0.1 | 1.0 ± 0.2 | 1.0 ± 0.3 | 2.8 ± 4.4 | 1.0 ± 0.1 | 1.0 ± 0.1 | 1.3 ± 0.2 | 1.0 ± 0.1 | 2.0 ± 1.3 | 1.9 ± 1.2 | |
| 14 | 1.0 ± 0.1 | 1.1 ± 0.2 | 0.9 ± 0.0 | 1.0 ± 0.4 | 1.3 ± 0.3 | 39.4 ± 43.1 | 1.0 ± 0.2 | 2.1 ± 1.2 | 1.6 ± 0.2 | 1.0 ± 0.4 | 1.7 ± 0.5 | 5.7 ± 3.0** | |
| Lcn2 (NGAL) | 1 | 1.0 ± 0.8 | 0.5 ± 0.1 | 0.6 ± 0.1 | 1.0 ± 0.6 | 0.8 ± 0.7 | 0.7 ± 0.4 | 1.0 ± 0.4 | 1.4 ± 0.2 | 1.1 ± 0.3 | 1.0 ± 0.9 | 2.6 ± 1.4 | 3.8 ± 2.4 |
| 3 | 1.0 ± 0.1 | 1.0 ± 0.1 | 0.9 ± 0.2 | 1.0 ± 0.4 | 1.0 ± 0.4 | 1.5 ± 1.5 | 1.0 ± 0.1 | 0.9 ± 0.4 | 1.0 ± 0.3 | 1.0 ± 0.2 | 3.6 ± 3.0 | 4.1 ± 2.6 | |
| 14 | 1.0 ± 0.4 | 0.7 ± 0.1 | 0.7 ± 0.1 | 1.0 ± 0.3 | 1.7 ± 0.3 | 81.6 ± 151.4 | 1.0 ± 0.3 | 2.4 ± 1.8 | 4.9 ± 2.5* | 1.0 ± 0.4 | 2.3 ± 1.2 | 6.2 ± 2.6** | |
| Timp-1 | 1 | 1.0 ± 0.3 | 1.2 ± 0.5 | 1.3 ± 0.3 | 1.0 ± 0.4 | 0.9 ± 0.4 | 0.7 ± 0.3 | 1.0 ± 0.5 | 1.2 ± 0.6 | 1.2 ± 0.5 | 1.0 ± 0.4 | 2.7 ± 1.1 | 3.7 ± 2.1 |
| 3 | 1.0 ± 0.2 | 1.2 ± 0.2 | 1.1 ± 0.6 | 1.0 ± 0.2 | 0.8 ± 0.5 | 1.4 ± 1.5 | 1.0 ± 0.4 | 1.0 ± 0.4 | 1.2 ± 0.5 | 1.0 ± 0.5 | 2.9 ± 1.7 | 2.3 ± 1.4 | |
| 14 | 1.0 ± 0.4 | 1.1 ± 0.3 | 1.1 ± 0.3 | 1.0 ± 0.3 | 1.0 ± 0.3 | 12.7 ± 12.1* | 1.0 ± 0.5 | 1.9 ± 1.2 | 1.5 ± 0.6 | 1.0 ± 0.9 | 2.9 ± 1.6 | 5.5 ± 2.9** | |
| OPN (secreted phosphoprotein 1) | 1 | 1.0 ± 0.6 | 0.7 ± 0.2 | 0.8 ± 0.3 | 1.0 ± 0.5 | 1.1 ± 0.7 | 1.0 ± 0.5 | 1.0 ± 0.5 | 1.1 ± 0.7 | 1.0 ± 0.5 | 1.0 ± 1.0 | 1.5 ± 0.8 | 2.6 ± 2.1 |
| 3 | 1.0 ± 0.1 | 1.2 ± 0.3 | 0.9 ± 0.1 | 1.0 ± 0.3 | 1.0 ± 0.3 | 1.1 ± 0.8 | 1.0 ± 0.3 | 1.0 ± 0.3 | 1.1 ± 0.8 | 1.0 ± 0.2 | 2.6 ± 2.3 | 3.6 ± 2.4 | |
| 14 | 1.0 ± 0.2 | 0.8 ± 0.2 | 0.8 ± 0.2 | 1.0 ± 0.3 | 1.3 ± 0.5 | 21.3 ± 21.6* | 1.0 ± 0.0 | 2.4 ± 1.2 | 5.1 ± 1.6*** | 1.0 ± 0.7 | 1.6 ± 0.6 | 4.8 ± 2.6** | |
| HO-1 (HMOX1) | 1 | 1.0 ± 0.1 | 1.0 ± 0.2 | 0.9 ± 0.1 | 1.0 ± 0.6 | 1.4 ± 1.2 | 0.9 ± 0.6 | 1.0 ± 0.1 | 1.1 ± 0.3 | 0.8 ± 0.2 | 1.0 ± 0.4 | 3.0 ± 0.8 | 7.1 ± 5.8 |
| 3 | 1.0 ± 0.1 | 1.0 ± 0.3 | 1.0 ± 0.2 | 1.0 ± 0.2 | 1.2 ± 0.3 | 1.2 ± 0.3 | 1.0 ± 0.4 | 0.7 ± 0.2 | 0.9 ± 0.1 | 1.0 ± 0.3 | 11.8 ± 9.9 | 13.7 ± 9.4* | |
| 14 | 1.0 ± 0.2 | 1.0 ± 0.2 | 1.3 ± 0.2 | 1.0 ± 0.3 | 1.5 ± 0.3 | 7.1 ± 8.2 | 1.0 ± 0.1 | 1.8 ± 0.3* | 3.4 ± 0.7*** | 1.0 ± 0.5 | 13.4 ± 7.6** | 14.7 ± 2.0** | |
| Vimentin | 1 | 1.0 ± 0.1 | 1.0 ± 0.1 | 1.0 ± 0.1 | 1.0 ± 0.4 | 1.0 ± 0.4 | 0.9 ± 0.3 | 1.0 ± 0.2 | 0.9 ± 0.1 | 0.9 ± 0.2 | 1.0 ± 0.3 | 1.3 ± 0.5 | 1.3 ± 0.4 |
| 3 | 1.0 ± 0.1 | 1.0 ± 0.2 | 0.9 ± 0.1 | 1.0 ± 0.1 | 1.0 ± 0.3 | 1.1 ± 0.3 | 1.0 ± 0.1 | 0.9 ± 0.1 | 0.9 ± 0.1 | 1.0 ± 0.3 | 3.9 ± 2.5 | 3.3 ± 2.4 | |
| 14 | 1.0 ± 0.1 | 0.9 ± 0.1 | 0.9 ± 0.0 | 1.0 ± 0.2 | 1.3 ± 0.4 | 3.4 ± 3.0 | 1.0 ± 0.2 | 1.0 ± 0.2 | 1.0 ± 0.1 | 1.0 ± 0.4 | 3.8 ± 1.8** | 3.4 ± 0.6* | |
Note. Data are presented as mean ± SD of five individual animals per dose group. Statistical analysis was performed by ANOVA and Dunnett’s test.
*p < 0.05, **p < 0.01, and ***p < 0.001.