Table 2. B12-related parameters measure in mice following 27 days of continuous delivery of saline (control), cobinamide (Cbi) and vitamin B12 (B12) by osmotic minipumps1.
ControlMedian (range) | Cbi2Median (range) | B122Median (range) | |
Haematological parameters in blood | |||
White blood cell count (10−9L) | 1.7 (1.4 – 2.6) | 2.6 (1.1 − 3.3) | 3.6 (2.04 − 6.0)* |
Red blood cell count (10−12L) | 9.4 (9.0 – 9.7) | 9.2 (9.1 – 9.5) | 9.6 (9.3 – 9.9) |
Haemoglobin (mM) | 9.6 (9.2 – 9.9) | 9.4 (9.0 – 9.9) | 9.8 (9.6 – 9.9) |
Erythrocyte volume fraction (ratio) | 0.50 (0.49 – 0.52) | 0.49 (0.47 – 0.51) | 0.50 (0.50 – 0.52) |
Erythrocyte mean cell volume (fL) | 53 (53 – 54) | 53 (52 – 54) | 53 (52 – 54) |
Erythrocyte mean cell haemoglobin concentration (mmol/L) | 19 (19 – 20) | 19 (19 – 20) | 19 (19 – 20) |
B12, Cbi and related biochemical parameters in plasma | |||
B12 (nmol/L) | 25 (21 – 30) | 19 (16 – 23)* | 160 (120 – 240)***,### |
Cbi (nmol/L) | <0.9 | 820 (650 – 1100)*** | <0.9### |
UB12BC (nmol/L) | 28.4 (23.8 – 31.8) | <2*** | <2***,### |
MMA (µmol/L) | 0.45 (0.29 – 0.62) | 0.50 (0.28 – 0.67) | 0.33 (0.23 – 0.42)*,# |
tHCY (µmol/L) | 6.6 (6.0 – 7.8) | 7.6 (5.6 – 9.8) | 7.9 (6.6 – 9.5)* |
Cysteine (µmol/L) | 200 (190 – 220) | 200 (190 – 250) | 220 (202 – 250)* |
Methionine (µmol/L) | 86 (55 – 98) | 83 (62 – 106) | 70 (66 – 99) |
B12, Cbi and creatinine in urine3 | |||
u–B12/u–Crea (nmol/mmol) | 3 (3 – 4) | 18 (10 – 29)** | 14 (6 – 85)×103 ***,### |
u–Cbi/u–Crea (nmol/mmol) | 1 (1 – 6) | 14. (7 – 21) x.103** | N.D.4 |
u–MMA/u–Crea (μmol/mmol) | 15 (10 – 28) | 20 (14 – 30) | 20 (13 – 29) |
u–crea (µmol/24 h) | 1.7 (1.3 – 2.4) | 1.1 (0.6 – 1.6)* | 1.1 (1.0 – 1.9) |
B12 and Cbi in tissues | |||
Kidney–B12 (pmol/g) | 1800 (1500 – 2100) | 590 (450 – 710)*** | 6900 (6000 – 9400)***;### |
Kidney–Cbi (pmol/g) | <50 | 2700 (1400 – 2900) ***;### | <50 |
Liver–B12 (pmol/g) | 320 (290 – 390) | 170 (140 – 200)*** | 530 (390 – 610)***;### |
Liver–Cbi (pmol/g) | <2 | 690 (630 – 920)***;### | <2 |
Salivary gland–B12 (pmol/g) | 130 (110 – 160) | 59 (18 –96)*** | 180 (150 – 290) *;### |
Salivary gland–Cbi (pmol/g) | <10 | 530 (240 – 920)***;### | <10 |
Salivary gland–UB12BC (pmol/g) | 79 (33 – 180) | 10 (1.2 – 16)* | 2.8 (1.0 – 16)* |
1: The listed values are obtained from samples collected from mice 27 days after subcutaneous insertion of an osmotic minipump delivering 0.9% NaCl (control), 4.25 nmol/h Cbi, or 1.75 nmol/h B12 in 7–week–old female mice of the 129.S6 strain. n = 7 in each group.
2: ANOVA tests are carried out between Control and Cbi– or B12–mice (*p<0.05; **p<0.001; ***p<0.0001) as well as between Cbi and B12 mice (#p<0.05; ##p<0.001; ###p<0.0001). For values below analytical detection limit, the detection limit has been used in the calculations.
3: n = 6 for urine values of control mice.
4: The used assay for analysis of Cbi in urine does not allow for determination of small amounts of Cbi in B12–rich samples.
ND: Not determined. tHcy: total homocysteine. UB12BC: Unsaturated B12 binding capacity. B12: Vitamin B12 Cbi: cobinamide. Crea: creatinine. MMA: methylmalonic acid.