TABLE 2

Toxicity study of ShK(L5) Data are expressed as mean ± S.D.

In vitro tests 100 nM ShK(L5)
Cytotoxicity (% dead cells)
Human PBMCs 7.5 ± 4.3
PAS T cells 8.1 ± 0.8
Jurkat cells 5.5 ± 3.3
Burkitt lymphoma 3.1 ± 0.9
RPMI 8226 myeloma 6.5 ± 2.1
Ames test Negative
Acute in vivo tests Saline ShK(L5) 10 μg/kg
Electrocardiograma
Heart rate 302 ± 13 311 ± 20
SDNN 13.3 ± 3.0 17.8 ± 4.4
CV% 6.7 ± 1.4 9.2 ± 2.2
SDANN5 min 5.0 ± 2.0 6.9 ± 2.3
rMSSD 6.8 ± 2.2 9.8 ± 3.5
HF (n.u.) 71 ± 21 79 ± 37
HF (%) 50 ± 8 53 ± 10
LF (n.u.) 68 ± 4 64 ± 10
LF (%) 50 ± 8 47 ± 10
LF/HF 1.1 ± 0.4 1.3 ± 0.7
Subchronic in vivo tests Saline ShK(L5) 10 μg/kg/day for 2 weeks
Weight gain (%) 7.2 ± 1.8 6.2 ± 1.7
Complete blood count
Hematocrit (%) 40.3 ± 1.4 39.0 ± 4.9
Hemoglobin (g/dl) 15.3 ± 0.5 15.0 ± 1.5
MCV (fl) 48.5 ± 0.2 48.3 ± 0.3
MCH (pg) 18.5 ± 0.8 18.5 ± 0.6
MCHC (g/dl) 38.0 ± 1.8 38.4 ± 1.3
Total white cells (×103/mm3) 7.1 ± 2.1 7.1 ± 2.5
Total red cells (×106/mm3) 8.3 ± 0.3 8.1 ± 1.0
Total platelets (×103/mm3) 656 ± 214 606 ± 106
Blood chemistry
Alkaline phosphatase (U/L) 170 ± 26 150 ± 18
Glucose (mg/dl) 139 ± 21 150 ± 18
Blood urea nitrogen (mg/dl) 17.1 ± 2.6 15.0 ± 1.7
Creatinine (mg/dl) 0.6 ± 0 0.6 ± 0.1
Albumin (g/dl) 5.0 ± 0.3 4.5 ± 0.4
Thymic cell populations (%)
CD4 CD8 3.6 ± 1.1 4.3 ± 0.7
CD4+ CD8+ 77.8 ± 6.1 76.8 ± 4.1
CD4+ CD8 8.5 ± 1.7 11.2 ± 2.0
CD4 CD8+ 10.0 ± 3.3 7.6 ± 1.3
CD3+ 89.5 ± 1.6 93.2 ± 3.5
Splenic populations (%)
CD3+ 72.4 ± 4.4 65.4 ± 0.1
CD3+ CD45RC+ 35.6 ± 2.6 39.8 ± 1.1
CD3+ CD45RC 23.6 ± 2.3 26.5 ± 1.3
CD3+ CD4+ 62.7 ± 0.1 66.6 ± 1.2
CD3+ CD8+ 26.9 ± 0.1 25.0 ± 0.2
IgM+ 38.8 ± 1.5 33.3 ± 0.3
  • SDNN, standard deviation of all normal-to-normal RR intervals; CV%, 100 × SDNN/average RR interval; SDANN5 min, standard deviation of the mean of normal RR intervals for each 5-min period; rMSSD, root-mean-square of successive difference; HF (n.u.), high frequency (0.75-2.5 Hz) power in normalized unit; LF (n.u.), low frequency (0.2-0.75 Hz) power in normalized unit; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration.

  • a Tested with t tests, P < 0.05 on all parameters.