Table 2.
MCLR Toxicity after 40 µg/kg i.p. (based on vendor label) in the CD-a mouse 1.
| Number of Animals | Liver Wt (g) | Liver/Bwt % | Weight Change (g) | Liver Score | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Vendor (µg/kg MCLR) | Male | Female | Male | Female | Male | Female | Male | Female | Male | Female |
| Control | 18 | 18 | 2.1 ± 0.1 | 1.4 ± 0.1 | 6.1 ± 0.15 | 5.4 ± 0.14 | −0.09 ± 0.08 | −0.19 ± 0.16 | 1.9 ± 0.35 | 1.2 ± 0.35 |
| A (13.2) | 12 | 12 | 2.0 ± 0.1 | 1.4 ± 0.0 | 5.7 ± 0.19 | 5.5 ± 0.17 | −0.41 ± 0.13 | −0.20 ± 0.15 | 3.0 ± 0.51 | 2.8 ± 0.52 a |
| B (25.6) | 12 | 12 | 2.1 ± 0.1 | 1.5 ± 0.1 | 6.0 ± 0.19 | 5.7 ± 0.17 | −0.20 ± 0.14 | −0.49 ± 0.11 | 4.3 ± 0.45 c | 2.9 ± 0.34 b |
| C (34.0) | 12 | 12 | 2.0 ± 0.1 | 1.5 ± 0.1 | 6.0 ± 0.19 | 5.9 ± 0.17 a | −0.12 ± 0.17 | −0.41 ± 0.19 | 5.7 ± 0.53 c | 3.1 ± 0.67 a |
| D (35.6) | 12 | 12 | 2.0 ± 0.1 | 1.5 ± 0.1 | 6.0 ± 0.20 | 5.9 ± 0.18 a | −0.44 ± 0.13 | −0.68 ± 0.34 a | 6.3 ± 0.57 c | 4.0 ± 0.62 c |
| E (39.6) | 12 | 12 | 1.9 ± 0.1 | 1.7 ± 0.1 c | 5.9 ± 0.19 | 6.2 ± 0.17 c | −0.17 ± 0.34 | −0.65 ± 0.25 | 7.3 ± 0.66 c | 4.5 ± 1.12 b |
| F (38.4) | 12 | 12 | 2.3 ± 0.1 a | 1.6 ± 0.1 | 7.0 ± 0.21 c | 6.2 ± 0.2 c | −0.18 ± 0.15 | −0.27 ± 0.27 | 5.6 ± 0.97 c | 6.6 ± 1.05 c |
| G (44.8) | 12 | 12 | 2.2 ± 0.1 | 2.0 ± 0.1 c | 6.6 ± 0.19 | 7.8 ± 0.20 c | −0.53 ± 0.22 | −0.24 ± 0.13 | 7.6 ± 0.94 c | 9.4 ± 0.43 c |
| ALT (IU/L) | AST (IU/L) | GLDH (IU/L) | BUN (mg/dL) | Creatinine (mg/dL) | ||||||
| Vendor (µg/kg MCLR) | Male | Female | Male | Female | Male | Female | Male | Female | Male | Female |
| Control | 33.4 ± 2.2 | 43.4 ± 6.7 | 69.0 ± 7.7 | 98.2 ± 10.9 | 13 ± 1.7 | 10.7 ± 1.2 | 11.1 ± 0.22 | 9.6 ± 0.27 | 0.48 ± 0.01 | 0.6 ± 0.06 |
| A (13.2) | 42.9 ± 3.9 | 89.2 ± 40.3 | 72.5 ± 9.1 | 142.1 ± 43.7 | 22.7 ± 5.2 | 13 ± 2.2 | 9.6 ± 0.46 a | 8.1 ± 0.39 a | 0.5 ± 0.00 | 0.5 ± 0.03 a |
| B (25.6) | 145.9 ± 22.3 b | 104.5 ± 27.8 b | 124 ± 2.5 | 140.8 ± 26.4 | 37.3 ± 8.1 a | 27.9 ± 5.0 b | 10.7 ± 0.87 | 9.2 ± 0.50 | 0.4 ± 0.01 a | 0.6 ± 0.05 |
| C (34.0) | 820.6 ± 395.1 c | 567.3 ± 431.2 b | 372.4 ± 218.0 a | 535.2 ± 407.7 | 108.2 ± 29.9 b | 28.6 ± 8.1 a | 9.9 ± 0.41 | 8.0 ± 0.40 b | 0.5 ± 0.01 | 0.7 ± 0.09 |
| D (35.6) | 743.1 ± 224.5 c | 676.5 ± 423.8 c | 276 ± 83.5 | 479.8 ± 283.7 a | 152.1 ± 32.6 c | 64.3 ± 7.6 c | 9.8 ± 0.25 a | 9.1 ± 0.34 | 0.5 ± 00 | 0.8 ± 0.10 |
| E (39.6) | 435.8 ± 166.4 c | 750.3 ± 403.7 c | 725.9 ± 553.2 b | 678.1 ± 441.2 b | 78.8 ± 23.8 b | 62.3 ± 16.0 c | 11.4 ± 1.08 | 9.1 ± 0.60 | 0.6 ± 0.08 | 0.6 ± 0.06 |
| F (38.4) | 864.1 ± 314.9 c | 715.4 ± 153.5 c | 328.1 ± 105.4 c | 681.2 ± 341.8 c | No data | 198.8 ± 44.3 c | 11.7 ± 0.67 | 9.6 ± 0.42 | 0.5 ± 0.05 | 0.4 ± 0.03 a |
| G (44.8) | 2467.2 ± 1089.4 c | 2997.4 ± 806.8 c | 962.6 ± 403.8 c | 2191.1 ± 1140.6 c | 81.1 ± 31.4 b | 72 ± 23.0 c | 10.3 ± 0.88 | 15.3 ± 1.76 c | 0.5 ± 0.02 | 0.8 ± 0.10 |
| Albumin (g/dL) | Globulin (g/dL) | Total Protein (g/dL) | Early Deaths | |||||||
| Vendor (µg/kg MCLR) | Male | Female | Male | Female | Male | Female | Male | Female | ||
| Control | 3.1 ± 0.04 | 3.6 ± 0.10 | 2.1 ± 0.03 | 2.1 ± 0.06 | 5.2 ± 0.06 | 5.3 ± 0.13 | 0 | 0 | ||
| A (13.2) | 3.1 ± 0.05 | 3.6 ± 0.14 | 2.2 ± 0.04 | 2.0 ± 0.05 | 5.2 ± 0.07 | 5.0 ± 0.18 | 0 | 0 | ||
| B (25.6) | 3.1 ± 0.06 | 3.8 ± 0.12 | 2.2 ± 0.11 | 2.2 ± 0.04 a | 5.2 ± 0.11 | 5.4 ± 0.19 | 0 | 0 | ||
| C (34.0) | 3.1 ± 0.05 | 3.7 ± 0.14 | 2.3 ± 0.03 b | 2.2 ± 0.07 | 5.4 ± 0.07 | 5.1 ± 0.19 | 0 | 0 | ||
| D (35.6) | 3.1 ± 0.06 | 3.6 ± 0.11 | 2.3 ± 0.04 | 2.5 ± 0.10 b | 5.3 ± 0.05 | 5.8 ± 0.10 | 0 | 0 | ||
| E (39.6) | 3.2 ± 0.05 a | 3.4 ± 0.12 | 2.3 ± 0.03 b | 1.9 ± 0.11 | 5.1 ± 0.17 | 5.0 ± 0.17 | 1 | 2 | ||
| F (38.4) | 2.9 ± 0.06 a | 3.5 ± 0.11 | 2.2 ± 0.08 | 2.3 ± 0.12 | 5.4 ± 0.11 a | 5.5 ± 0.16 | 3 | 1 | ||
| G (44.8) | 3.0 ± 0.06 | 3.1 ± 0.11 c | 2.2 ± 0.06 a | 1.7 ± 0.14 b | 5.0 ± 0.15 | 4.8 ± 0.33 | 2 | 7 | ||
1 All significance tests of difference from control. Mortality statistical significance by Fisher’s exact test; liver score by Cochran–Mantel–Haenszel chi-square; all other endpoints by ANOVA/t-test. MCLR dose is based on measurement by MS-TOF. a = p ≤ 0.05 for differences from controls. b = p ≤ 0.01 for differences from controls. c = p ≤ 0.001 for differences from controls.