Supporting Information Control Low dose (15 mg/kg/day) High dose (60 mg/kg/day) Fe Mo Composite Zn Figure S1. The distribution of Fe, Mo and Zn and composite images (red: Fe, green: Zn, blue: Mo) in rat kidney sections. Left: Kidney section (4 µm) from a control animal; Middle: Kidney section (20 µm) from a rat given 15 mg/kg/day TTM; Right: Kidney section (4 µm) from a rat given 60 mg/kg/day TTM. The colour scale indicates the concentration of Mo in tissue in mg kg−1 and the intensities of 56Fe and 64Zn signals in counts per pixel. Control Low dose (15 mg/kg/day) High dose (60 mg/kg/day) Cu Mo Composite Zn Figure S2. The distribution of Cu, Mo and Zn and composite images (red: Cu, green: Zn, blue: Mo) in rat kidney sections. Left: Kidney section (4 µm) from a control animal; Middle: Kidney section (20 µm) from a rat given 15 mg/kg/day TTM; Right: Kidney section (4 µm) from a rat given 60 mg/kg/day TTM. The colour scale indicates the concentrations of Cu and Mo in tissue in mg kg−1 and the intensity of 64Zn signals in counts per pixel. 30% Fraction of pixels 25% Control group (G3) Low-dosage group (G2) High-dosage group (G1) 20% 15% 10% 5% 0% 1.3 5 9 12 16 20 23 27 31 -1 Concentration of Mo, mg kg Figure S3. Average histograms of Mo distribution in liver sections taken from three rats in each of the TTM dosage groups. Error bars correspond to 1sd (n=3). 20 18 16 Control group (G3) Low-dosage group (G2) High-dosage group (G1) Fraction of pixels, % 14 12 10 8 6 4 2 0 1 7 13 19 25 31 37 43 49 55 61 Concentration of Mo, mg kg-1 67 73 79 Figure S4. Average histograms of Mo distribution in spleen sections taken from three rats in each of the TTM dosage groups. Error bars correspond to 1sd (n=3). Cu Mo Zn Composite Figure S5. The distribution of Cu, Mo and Zn and a composite image (red: Cu, green: Zn, blue: Mo) in a 20 µm brain section of a rat administered with 15 mg TTM/kg/day (see Fig. 12). The colour scale indicates the concentrations of Cu and Mo in tissue in mg kg−1 and the intensity of 64Zn signals in counts per pixel. 45% 40% Fraction of pixels 35% Control group (G3) Low-dosage group (G2) High-dosage group (G1) 30% 25% 20% 15% 10% 5% 0% 1 4 6 8 11 13 16 18 20 23 Concentration of Mo, mg kg-1 25 28 30 Figure S6. Average histograms of Mo distribution in brain sections taken from three rats from each of the TTM dosage groups. Error bars correspond to 1sd (n=3). Table S1. Summary of clinical biochemistry parameters in male rats following treatment with bis-choline tetrathiomolybdate. Male Test Parameters A/G GGT (U/L) PA (mg/L) TBIL (umol/L) DBIL (umol/L) TP (g/L) ALB (g/L) GLB (g/L) ALT (U/L) AST (U/L) ALP (U/L) LDH (U/L) BUN (mmol/L) CR (µmol/L) Groups G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 Pre-dose 1.53 ± 0.05 1.57 ± 0.04 1.53 ± 0.03 0.90 ± 0.18 0.83 ± 0.22 0.63 ± 0.11 21.1 ± 0.9 20.2 ± 0.6 18.4 ± 1.4 <LOD <LOD <LOD <LOD <LOD <LOD 60.7 ± 1.3 58.2 ± 1.3 59.0 ± 0.6 36.6 ± 0.7 35.5 ± 0.7 35.7 ± 0.4 24.1 ± 0.7 22.7 ± 0.7 23.3 ± 0.4 58.2 ± 3.2 51.9 ± 3.7 53.4 ± 3.5 162 ± 12 143 ± 13 125 ± 10 380 ± 14 398 ± 33 404 ± 25 1950 ± 337* 1273 ± 240 897 ± 171 5.09 ± 0.16** 5.61 ± 0.23 6.50 ± 0.31 16.0 ± 1.3 16.0 ± 1.3 16.0 ± 2.0 Treatment 4 weeks 1.22 ± 0.03 1.28 ± 0.03 1.23 ± 0.03 1.15 ± 0.33 1.38 ± 0.28 0.85 ± 0.23 43.1 ± 1.5 35.4 ± 1.8 41.3 ± 4.9 2.42 ± 0.19** 1.98 ± 0.10** 0.25 ± 0.08 0.88 ± 0.06** 0.92 ± 0.05** 0.48 ± 0.03 69.0 ± 0.9* 66.8 ± 1.5 66.3 ± 0.5 37.9 ± 0.3** 37.7 ± 0.6 36.4 ± 0.3 31.1 ± 0.8 29.1 ± 1.0 29.9 ± 0.5 57.4 ± 4.1 51.1 ± 3.1 45.8 ± 2.6 106 ± 4 109 ± 3 103 ± 11 242 ± 8 266 ± 27 238 ± 12 631 ± 116 648 ± 113 516 ± 168 4.87 ± 0.23 5.16 ± 0.50 5.26 ± 0.41 38.8 ± 1.6 45.3 ± 1.4 42.7 ± 2.8 8 weeks 1.18 ± 0.04 1.22 ± 0.03 1.17 ± 0.02 1.03 ± 0.13 1.05 ± 0.29 0.52 ± 0.15 3.3 ± 0.9 0.9 ± 0.2 2.5 ± 1.0 3.43 ± 0.22** 2.77 ± 0.29** 0.43 ± 0.14 1.03 ± 0.09* 1.10 ± 0.07** 0.68 ± 0.05 71.1 ± 1.3 70.1 ± 1.6 68.3 ± 0.5 38.5 ± 0.6 38.8 ± 0.5* 36.7 ± 0.4 32.6 ± 1.1 31.4 ± 1.1 31.6 ± 0.5 56.0 ± 3.2 52.4 ± 4.1 49.1 ± 2.9 97 ± 8 111 ± 8 101 ± 8 172 ± 10 189 ± 20 162 ± 9 362 ± 88 653 ± 114 467 ± 170 6.03 ± 0.18* 5.45 ± 0.41 5.16 ± 0.15 24.2 ± 0.9** 30.8 ± 1.2 31.5 ± 1.0 12 weeks 1.20 ± 0.03 1.22 ± 0.03 1.15 ± 0.02 0.53 ± 0.07 0.38 ± 0.12 0.60 ± 0.12 4.0 ± 0.6 3.3 ± 0.5 3.0 ± 0.7 3.37 ± 0.18** 2.57 ± 0.24** 0.30 ± 0.05 1.35 ± 0.14** 1.17 ± 0.07** 0.53 ± 0.03 71.1 ± 1.2 69.8 ± 1.2 69.8 ± 0.7 38.7 ± 0.5 38.2 ± 0.5 37.1 ± 0.6 32.4 ± 1.0 31.6 ± 0.8 32.7 ± 0.5 53.4 ± 4.5 45.9 ± 2.8 41.2 ± 2.9 159 ± 15 150 ± 10 145 ± 16 133 ± 7 145 ± 19 118 ± 7 2141 ± 392 2171 ± 215 1688 ± 223 6.20 ± 0.25* 5.38 ± 0.21 5.25 ± 0.21 24.2 ± 1.0 26.0 ± 0.8 26.7 ± 0.8 UA (µmol/L) ADA (U/L) G1 G2 G3 G1 G2 G3 96.2 ± 5.8 80.9 ± 6.3 88.3 ± 5.7 23.0 ± 9.7 25.0 ± 14.0 12.8 ± 5.0 92.0 ± 11.8 83.9 ± 8.3 70.5 ± 9.2 29.6 ± 15.3 59.1 ± 33.2 23.8 ± 9.3 65.3 ± 7.0 75.6 ± 8.2 81.5 ± 9.1 22.3 ± 7.6 43.3 ± 26.8 19.9 ± 9.4 96.9 ± 11.9 79.1 ± 6.9 81.1 ± 6.9 17.8 ± 5.4 34.2 ± 21.9 18.4 ± 6.2 Notes: G1 = 60 mg/kg/day; G2 = 15 mg/kg/day; G3 = vehicle control. A/G = albumin to globulin ratio; GGT = gamma-glutamyltransferase; PA = pre albumin; TBil = total bilirubin; DBil = unconjugated bilirubin; TP = total protein; ALB = albumin; GLB = globulin; ALT = alanine aminotransaminase; AST = aspartate aminotransaminase; ALP = alkaline phosphatase; LDH = lactate dehydrogenase: BUN = blood urea nitrogen; CRE = creatinine; UA = uric acid; ADA = adenosine deaminase. Values are expressed as mean ± SE of 6 rats in each group. * and ** indicate a significant difference at p < 0.05 and p < 0.01 level, respectively, when compared to G3 (vehicle control group). <LOD means that the values are beneath the limit of detection. Table S2: Summary of clinical biochemistry parameters in female rats following treatment with bis-choline tetrathiomolybdate. Female Test Parameters A/G GGT (U/L) PA (mg/L) TBIL (µmol/L) DBIL (µmol/L) TP (g/L) ALB (g/L) GLB (g/L) ALT (U/L) Groups G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 Pre-dose 1.72 ± 0.04 1.65 ± 0.05 1.68 ± 0.05 0.63 ± 0.14 0.83 ± 0.15* 0.23 ± 0.05 <LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD <LOD 64.9 ± 1.4 61.6 ± 0.8 62.7 ± 1.1 41.1 ± 0.7 38.2 ± 0.6 39.4 ± 0.9 23.8 ± 0.7 23.4 ± 0.5 23.3 ± 0.4 50.8 ± 2.3 51.3 ± 6.6 56.7 ± 2.3 159 ± 7* Treatment 4 weeks 1.37 ± 0.03 1.37 ± 0.03 1.37 ± 0.04 1.75 ± 0.32 1.73 ± 0.20 1.35 ± 0.45 35.9 ± 3.3 37.1 ± 2.6 37.3 ± 3.6 3.43 ± 0.31** 2.70 ± 0.16** 0.48 ± 0.14 1.05 ± 0.10** 0.80 ± 0.04* 0.58 ± 0.06 74.4 ± 1.4 72.7 ± 1.4 71.6 ± 0.6 43.0 ± 1.1 41.9 ± 1.0 41.3 ± 0.6 31.4 ± 0.4 30.8 ± 0.6 30.3 ± 0.6 67.8 ± 11.4 48.1 ± 1.1 59.4 ± 13.2 110 ± 5 8 weeks 1.37 ± 0.02 1.33 ± 0.02 1.38 ± 0.03 0.68 ± 0.14 0.82 ± 0.10 0.55 ± 0.24 <LOD <LOD 2.2 ± 0.6 3.87 ± 0.32** 2.95 ± 0.15** 0.95 ± 0.14 1.05 ± 0.11* 0.73 ± 0.06 0.63 ± 0.07 78.8 ± 1.7 76.5 ± 1.4 75.6 ± 1.8 45.7 ± 1.2 43.8 ± 1.0 43.6 ± 1.2 33.1 ± 0.6 32.6 ± 0.6 32.0 ± 0.7 68.7 ± 15.7 45.1 ± 1.5 63.5 ± 10.1 134 ± 23 12 weeks 1.42 ± 0.02 1.38 ± 0.03 1.38 ± 0.03 0.62 ± 0.22 0.45 ± 0.10 0.28 ± 0.10 3.3 ± 0.8 4.3 ± 0.2 5.4 ± 0.7 4.13 ± 0.18** 3.73 ± 0.43** 1.28 ± 0.21 1.08 ± 0.08* 1.03 ± 0.09* 0.68 ± 0.09 77.6 ± 1.1 75.4 ± 1.6 77.4 ± 2.4 45.5 ± 0.6 43.7 ± 1.1 45.1 ± 1.5 32.1 ± 0.6 31.7 ± 0.6 32.3 ± 1.0 56.5 ± 8.8 43.0 ± 5.7 45.2 ± 5.8 144 ± 16 AST (U/L) ALP (U/L) LDH (U/L) BUN (mmol/L) CR (µmol/L) UA (µmol/L) ADA (U/L) G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 144 ± 18 121 ± 12 172 ± 12 190 ± 21 196 ± 17 1799 ± 111* 1162 ± 155 859 ± 220 6.13 ± 0.25 6.11 ± 0.43 6.35 ± 0.19 22.0 ± 2.0 19.0 ± 1.0 22.0 ± 1.3 93.1 ± 2.2* 91.0 ± 10.0 77.9 ± 4.0 52.1 ± 22.4 32.0 ± 11.2 27.1 ± 8.3 113 ± 7 149 ± 25 95 ± 7 107 ± 12 96 ± 9 619 ± 77 555 ± 82 875 ± 114 6.03 ± 0.33 6.97 ± 0.49 6.25 ± 0.21 34.5 ± 2.6** 44.3 ± 3.0 46.8 ± 1.5 80.5 ± 7.5 84.9 ± 6.4 76.0 ± 4.9 34.8 ± 16.2 17.8 ± 5.7 19.6 ± 7.6 140 ± 33 164 ± 36 60 ± 6 68 ± 10 64 ± 4 813 ± 192 561 ± 112 517 ± 135 7.28 ± 0.22 7.62 ± 0.58 6.33 ± 0.52 28.2 ± 1.9 33.7 ± 2.1 36.8 ± 2.7 76.4 ± 6.0 64.6 ± 2.4 60.6 ± 4.7 12.6 ± 5.7 11.2 ± 4.9 4.9 ± 1.1 140 ± 41 141 ± 25 48 ± 5 50 ± 6 46 ± 3 1212 ± 158 857 ± 214 1262 ± 250 6.68 ± 0.23 6.95 ± 0.60 5.93 ± 0.33 26.0 ± 1.8* 42.8 ± 9.5 32.0 ± 1.2 64.1 ± 6.8 167.4 ± 89.6 82.6 ± 19.9 13.8 ± 5.7 11.9 ± 4.4 4.7 ± 0.9 Notes: G1 = 60 mg/kg/day; G2 = 15 mg/kg/day; G3 = vehicle control. A/G = albumin to globulin ratio; GGT = gamma-glutamyltransferase; PA = pre albumin; TBil = total bilirubin; DBil = unconjugated bilirubin; TP = total protein; ALB = albumin; GLB = globulin; ALT = alanine aminotransaminase; AST = aspartate aminotransaminase; ALP = alkaline phosphatase; LDH = lactate dehydrogenase; BUN = blood urea nitrogen; CRE = creatinine; UA = uric acid; ADA = adenosine deaminase. Values are expressed as mean ± SE of 6 rats in each group. * and ** indicates a significant difference at p < 0.05 and p < 0.01 level, respectively, when compared to G3 (vehicle control group). <LOD means that the values are beneath the limit of detection Table S3. Hematological parameters of male animals treated with bis-choline tetrathiomolybdate. Test Parameters WBC (109/L) NEU (%) LYM (%) MON (%) EOS (%) Male Groups G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 Pre-dose 13.8 ± 1.0 12.0 ± 1.2 11.4 ± 0.6 10.4 ± 1.4 11.9 ± 1.4 12.1 ± 1.6 87.1 ± 1.7 85.5 ± 1.6 85.0 ± 1.6 1.92 ± 0.26 1.98 ± 0.27 2.10 ± 0.23 0.48 ± 0.10 0.62 ± 0.09 0.70 ± 0.15 0.08 ± 0.02 Treatment 4 weeks 14.8 ± 1.3 13.3 ± 2.0 10.3 ± 0.4 12.0 ± 2.1 10.9 ± 1.5 13.9 ± 1.6 85.3 ± 2.1 84.6 ± 2.1 82.7 ± 1.9 1.97 ± 0.16 2.58 ± 0.31 2.15 ± 0.16 0.65 ± 0.13 1.82 ± 0.95 1.23 ± 0.29 0.12 ± 0.02 8 weeks 12.3 ± 1.2 11.6 ± 2.0 9.8 ± 0.9 10.5 ± 1.2 12.4 ± 1.6 14.4 ± 2.4 86.1 ± 1.1 83.6 ± 1.6 81.7 ± 2.6 2.43 ± 0.36 3.00 ± 0.36 2.27 ± 0.44 0.98 ± 0.14 1.00 ± 0.13 1.53 ± 0.31 0.05 ± 0.02 12 weeks 11.1 ± 1.1 10.2 ± 1.0 8.7 ± 0.9 12.8 ± 2.0 14.9 ± 1.7 16.3 ± 1.5 83.2 ± 2.5 80.8 ± 1.8 79.8 ± 1.5 3.03 ± 0.46 3.20 ± 0.38 2.55 ± 0.26 0.97 ± 0.15 1.07 ± 0.14 1.35 ± 0.23 0.03 ± 0.02 G2 G3 G1 NEU (109/L) G2 G3 G1 LYM (109/L) G2 G3 G1 9 MON (10 /L) G2 G3 G1 9 G2 EOS (10 /L) G3 G1 9 BAS (10 /L) G2 G3 G1 12 RBC (10 /L) G2 G3 G1 HGB (g/L) G2 G3 G1 HCT G2 (%) G3 G1 MCV G2 (fL) G3 G1 MCH G2 (pg) G3 G1 MCHC (g/L) G2 G3 G1 RDW-SD (fL) G2 G3 G1 RDW-CV (%) G2 G3 G1 PLT (109/L) G2 G3 G1 MPV G2 (fL) G3 G1 PCT G2 (%) G3 BAS (%) 0.07 ± 0.02 0.07 ± 0.02 1.40 ± 0.16 1.35 ± 0.09 1.42 ± 0.22 12.02 ± 0.98 10.30 ± 1.24 9.68 ± 0.43 0.27 ± 0.04 0.22 ± 0.03 0.23 ± 0.03 0.06 ± 0.01 0.07 ± 0.01 0.08 ± 0.02 0.01 ± 0.00 0.01 ± 0.00 0.01 ± 0.00 7.07 ± 0.17 6.92 ± 0.27 6.91 ± 0.13 144 ± 5 141 ± 4 144 ± 3 43.6 ± 1.1 42.8 ± 1.2 43.7 ± 0.7 61.7 ± 0.6 62.0 ± 0.9 63.3 ± 0.7 20.3 ± 0.3 20.4 ± 0.3 20.9 ± 0.2 329 ± 3 329 ± 2 330 ± 2 30.0 ± 1.0 29.2 ± 0.5 30.6 ± 0.7 14.0 ± 0.5 13.7 ± 0.2 13.9 ± 0.3 989 ± 57 984 ± 53 870 ± 79 8.17 ± 0.09 8.13 ± 0.11 8.30 ± 0.12 0.81 ± 0.04 0.80 ± 0.05 0.72 ± 0.07 0.12 ± 0.02 0.05 ± 0.02 1.67 ± 0.22 1.38 ± 0.21 1.43 ± 0.20 12.68 ± 1.34* 11.42 ± 1.90 8.47 ± 0.16 0.28 ± 0.04 0.30 ± 0.04 0.23 ± 0.02 0.09 ± 0.01 0.19 ± 0.07 0.13 ± 0.03 0.02 ± 0.00** 0.02 ± 0.00* 0.01 ± 0.00 8.72 ± 0.18* 8.62 ± 0.16* 8.11 ± 0.06 170 ± 3 168 ± 3 161 ± 1 49.9 ± 0.9* 49.2 ± 0.7* 46.8 ± 0.4 57.2 ± 0.5 57.1 ± 0.7 57.7 ± 0.7 19.5 ± 0.3 19.5 ± 0.2 19.9 ± 0.2 341 ± 3 342 ± 1 345 ± 2 24.6 ± 0.5 24.6 ± 0.3* 25.9 ± 0.3 14.5 ± 0.4 14.4 ± 0.4 14.0 ± 0.3 908 ± 40 693 ± 105 954 ± 48 8.65 ± 0.12 8.47 ± 0.06 8.33 ± 0.07 0.78 ± 0.04 0.59 ± 0.09 0.80 ± 0.04 0.03 ± 0.02 0.10 ± 0.06 1.28 ± 0.21 1.32 ± 0.15 1.40 ± 0.26 10.55 ± 1.03 9.77 ± 1.77 7.98 ± 0.77 0.32 ± 0.07 0.38 ± 0.13 0.25 ± 0.06 0.11 ± 0.01 0.11 ± 0.02 0.16 ± 0.04 0.01 ± 0.00 0.00 ± 0.00 0.01 ± 0.01 8.88 ± 0.18 8.98 ± 0.15* 8.19 ± 0.22 162 ± 2 166 ± 2* 154 ± 3 48.0 ± 0.6* 48.5 ± 0.7** 45.0 ± 0.6 54.1 ± 0.7 54.1 ± 0.8 55.1 ± 0.9 18.3 ± 0.2 18.5 ± 0.2 18.9 ± 0.2 338 ± 2 342 ± 1 343 ± 3 24.8 ± 0.7 25.6 ± 0.7 26.2 ± 0.5 16.2 ± 0.2 16.6 ± 0.1 15.7 ± 0.5 789 ± 46 837 ± 47 858 ± 65 8.00 ± 0.11 7.95 ± 0.06 8.02 ± 0.13 0.63 ± 0.04 0.67 ± 0.04 0.69 ± 0.06 0.02 ± 0.02 0.02 ± 0.02 1.37 ± 0.21 1.53 ± 0.21 1.42 ± 0.17 9.28 ± 1.09 8.28 ± 0.83 6.92 ± 0.74 0.33 ± 0.06 0.30 ± 0.03 0.22 ± 0.03 0.10 ± 0.01 0.11 ± 0.02 0.12 ± 0.03 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 8.96 ± 0.15 9.29 ± 0.24 8.71 ± 0.10 165 ± 3 169 ± 3 162 ± 2 48.1 ± 0.7 49.5 ± 1.0 47.4 ± 0.4 53.7 ± 0.5 53.4 ± 0.7 54.5 ± 0.8 18.4 ± 0.2 18.2 ± 0.3 18.6 ± 0.3 343 ± 3 342 ± 1 341 ± 1 24.2 ± 0.3* 24.8 ± 0.6 26.2 ± 0.5 15.9 ± 0.2 16.7 ± 0.3 16.4 ± 0.2 745 ± 111 791 ± 43 858 ± 83 8.54 ± 0.20 8.30 ± 0.11 8.38 ± 0.10 0.73 ± 0.04 0.66 ± 0.04 0.72 ± 0.07 PDW (%) P-LCR (%) G1 G2 G3 G1 G2 G3 8.88 ± 0.15 8.73 ± 0.19 9.22 ± 0.24 11.0 ± 0.7 10.8 ± 0.8 12.0 ± 1.0 10.25 ± 0.17* 9.55 ± 0.20 9.48 ± 0.20 14.3 ± 1.0 12.9 ± 0.5 11.7 ± 0.5 9.13 ± 0.17 8.97 ± 0.14 8.87 ± 0.22 9.7 ± 0.9 9.2 ± 0.4 9.4 ± 0.9 10.18 ± 0.32 9.65 ± 0.23 9.67 ± 0.20 13.6 ± 1.7 11.7 ± 0.8 12.3 ± 0.9 Notes: Values are expressed as mean ± SE of 6 rats in each group. * and ** indicates a significant difference at p < 0.05 and p < 0.01 level, respectively, when compared to G3 (vehicle control group). WBC = white blood cells; NEU = neutrophils; LYM = lymphocytes; MON = monocytes; EOS = eosinophils; BAS = basophils; RBC = red blood cells; HGB = ; HCT = hematocrit; MCV = mean corpuscular volume; MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin content; RDW-SD = red blood cell distribution width standard deviation; RDW-CV = coefficient of variation in erythrocyte distribution width; PLT = platelets; PDW = platelet distribution width; P-LCR = large platelet ratio. Table S4. Hematological parameters of female animals treated with bis-choline tetrathiomolybdate Test Parameters WBC (109/L) NEU (%) LYM (%) MON (%) EOS (%) BAS (%) NEU (109/L) LYM (109/L) MON (109/L) EOS (109/L) Female Groups G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 G1 G2 G3 Treatment 4 weeks 14.1 ± 1.0 10.0 ± 0.7 8.7 ± 0.6 7.2 ± 0.3 9.6 ± 0.8 8.5 ± 0.4 9.3 ± 0.5 7.3 ± 1.0 13.7 ± 1.2 11.2 ± 2.0 13.8 ± 2.2 14.9 ± 3.3 88.2 ± 0.7 89.7 ± 1.1 83.2 ± 1.2 84.9 ± 2.2 82.7 ± 2.4 81.2 ± 3.6 1.78 ± 0.25 1.80 ± 0.28 1.70 ± 0.28 2.30 ± 0.38 2.32 ± 0.27 2.40 ± 0.46 0.67 ± 0.10 1.08 ± 0.30 1.33 ± 0.18 1.55 ± 0.25 1.20 ± 0.25 1.43 ± 0.27 0.12 ± 0.02* 0.05 ± 0.02 0.05 ± 0.02 0.13 ± 0.02* 0.03 ± 0.02 0.05 ± 0.02 1.30 ± 0.08 0.72 ± 0.07 1.22 ± 0.15 0.78 ± 0.11 1.32 ± 0.24 1.25 ± 0.28 12.45 ± 0.95** 8.98 ± 0.70 7.23 ± 0.49 6.13 ± 0.34 8.00 ± 0.74 6.87 ± 0.46 0.27 ± 0.03 0.17 ± 0.03 0.15 ± 0.02 0.15 ± 0.02 0.22 ± 0.03 0.22 ± 0.05 0.10 ± 0.01 0.10 ± 0.02 0.12 ± 0.02 0.11 ± 0.02 0.11 ± 0.02 0.12 ± 0.02 Pre-dose 8 weeks 7.0 ± 0.5 4.8 ± 0.5 6.5 ± 0.6 11.3 ± 1.9 20.1 ± 3.5 15.3 ± 2.5 85.4 ± 2.6 75.5 ± 3.1 80.5 ± 2.9 1.83 ± 0.62 2.22 ± 0.21 2.40 ± 0.35 1.48 ± 0.29 1.98 ± 0.37 1.78 ± 0.32 0.02 ± 0.02 0.17 ± 0.10 0.00 ± 0.00 0.82 ± 0.18 0.90 ± 0.13 0.95 ± 0.11 5.93 ± 0.41 3.63 ± 0.49 5.30 ± 0.59 0.13 ± 0.05 0.12 ± 0.02 0.15 ± 0.02 0.10 ± 0.02 0.10 ± 0.02 0.11 ± 0.01 12 weeks 7.9 ± 1.0 5.3 ± 0.3 5.1 ± 0.8 11.8 ± 2.9 15.0 ± 2.5 12.9 ± 1.8 84.8 ± 3.1 79.7 ± 2.1 83.7 ± 2.0 2.07 ± 0.34 2.62 ± 0.25 1.82 ± 0.34 1.27 ± 0.19 2.65 ± 1.24 1.60 ± 0.15 0.03 ± 0.02 0.03 ± 0.03 0.02 ± 0.02 0.87 ± 0.17 0.78 ± 0.14 0.60 ± 0.07 6.82 ± 1.03 4.15 ± 0.24 4.30 ± 0.79 0.17 ± 0.03 0.13 ± 0.02 0.08 ± 0.03 0.10 ± 0.02 0.14 ± 0.07 0.08 ± 0.01 G1 BAS (109/L) G2 G3 G1 RBC (1012/L) G2 G3 G1 HGB (g/L) G2 G3 G1 HCT G2 (%) G3 G1 MCV G2 (fL) G3 G1 MCH G2 (pg) G3 G1 MCHC (g/L) G2 G3 G1 RDW-SD (fL) G2 G3 G1 RDW-CV (%) G2 G3 G1 PLT (109/L) G2 G3 G1 MPV G2 (fL) G3 G1 PCT G2 (%) G3 G1 PDW G2 (%) G3 G1 P-LCR (%) G2 G3 0.02 ± 0.00* 0.01 ± 0.00 0.00 ± 0.00 7.60 ± 0.22 7.35 ± 0.18 7.77 ± 0.28 156 ± 2 147 ± 5 153 ± 4 45.0 ± 1.4 42.9 ± 1.1 44.6 ± 1.2 59.2 ± 0.5 58.4 ± 0.4 57.6 ± 0.6 20.6 ± 0.4 20.0 ± 0.2 19.8 ± 0.2 348 ± 7 342 ± 4 343 ± 2 25.4 ± 0.2 25.0 ± 0.4 24.5 ± 0.4 12.6 ± 0.2 12.6 ± 0.2 12.9 ± 0.4 621 ± 141 823 ± 44 845 ± 85 8.02 ± 0.10 7.92 ± 0.10 7.93 ± 0.11 0.50 ± 0.11 0.65 ± 0.04 0.67 ± 0.07 8.74 ± 0.25 8.48 ± 0.12 8.67 ± 0.19 10.2 ± 0.7 9.2 ± 0.6 9.3 ± 0.9 0.01 ± 0.00 0.01 ± 0.00 0.01 ± 0.00 7.70 ± 0.25 7.80 ± 0.17 8.07 ± 0.13 153 ± 5 154 ± 3 158 ± 2 45.0 ± 1.1 44.9 ± 0.9 45.6 ± 0.5 58.5 ± 0.8 57.5 ± 0.2 56.5 ± 0.6 19.9 ± 0.2 19.7 ± 0.1 19.5 ± 0.2 341 ± 3 343 ± 1 346 ± 3 25.4 ± 0.4 25.1 ± 0.3 24.1 ± 0.4 13.1 ± 0.2 13.1 ± 0.3 13.3 ± 0.3 873 ± 22 835 ± 42 790 ± 82 8.37 ± 0.12 8.42 ± 0.10 8.17 ± 0.11 0.73 ± 0.01 0.70 ± 0.03 0.65 ± 0.07 9.45 ± 0.27 9.52 ± 0.14 9.05 ± 0.19 11.8 ± 0.9 12.4 ± 0.8 10.4 ± 0.7 0.00 ± 0.00 0.01 ± 0.01 0.00 ± 0.00 7.09 ± 0.08** 7.62 ± 0.39 8.21 ± 0.20 138 ± 1** 147 ± 7 156 ± 4 40.9 ± 0.4** 42.5 ± 2.1 45.2 ± 0.9 57.8 ± 0.7* 55.7 ± 0.3 55.0 ± 0.5 19.5 ± 0.1 19.3 ± 0.1 19.0 ± 0.1 338 ± 2** 346 ± 2 346 ± 2 25.2 ± 0.5* 24.1 ± 0.3 23.3 ± 0.4 12.7 ± 0.2 13.3 ± 0.2 13.3 ± 0.3 774 ± 25 669 ± 92 747 ± 57 8.02 ± 0.10 7.97 ± 0.08 7.92 ± 0.07 0.62 ± 0.02 0.54 ± 0.07 0.59 ± 0.04 8.68 ± 0.19 8.68 ± 0.14 8.82 ± 0.19 9.5 ± 0.9 9.2 ± 0.7 8.9 ± 0.6 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 7.73 ± 0.18 7.82 ± 0.18 7.97 ± 0.14 153 ± 3 151 ± 4 151 ± 3 44.9 ± 0.6 44.1 ± 1.0 44.4 ± 0.6 58.1 ± 0.6* 56.5 ± 0.4 55.7 ± 0.5 19.8 ± 0.1** 19.3 ± 0.1 18.9 ± 0.1 341 ± 2 341 ± 2 340 ± 3 25.6 ± 0.5 25.8 ± 0.2 24.9 ± 0.4 13.2 ± 0.4 14.1 ± 0.5 13.9 ± 0.2 754 ± 57 673 ± 116 783 ± 31 8.42 ± 0.10 8.53 ± 0.19 8.27 ± 0.11 0.63 ± 0.04 0.57 ± 0.09 0.65 ± 0.03 9.58 ± 0.21 10.03 ± 0.54 9.25 ± 0.19 12.3 ± 0.9 13.5 ± 1.5 11.0 ± 0.8 Notes: Values are expressed as mean ± SE of 6 rats in each group. * and ** indicates a significant difference at p < 0.05 and p < 0.01 level, respectively, when compared to G3 (vehicle control group). WBC = white blood cells; NEU = neutrophils; LYM = lymphocytes; MON = monocytes; EOS = eosinophils; BAS = basophils; RBC = red blood cells; HGB = ; HCT = hematocrit; MCV = mean corpuscular volume; MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin content; RDW-SD = red blood cell distribution width standard deviation; RDW-CV = coefficient of variation in erythrocyte distribution width; PLT = platelets; PDW = platelet distribution width; P-LCR = large platelet ratio.