Background
Methods
Asdamarin
High performance liquid chromatography (HPLC) analysis
Chemicals and animals
Determination of gastric emptying by phenol red method
Acute oral toxicity of Asdamarin
Sub-acute oral toxicity
Statistical analysis
Results
HPLC analysis of Asdamarin
Effect of Asdamarin on gastric emptying
Acute oral toxicity
Sub-acute oral toxicity
Body weight, food and water consumption
Sex | Day | Control | 250 mg/kg | 500 mg/kg | 1000 mg/kg | 1000 mg/kg reversal |
---|---|---|---|---|---|---|
Male | 7 | 17.83 ± 0.95 | 16.8 ± 0.42 | 18.31 ± 0.7 | 18.19 ± 0.61 | 21.7 ± 0.86 |
14 | 18.8 ± 0.36 | 17.72 ± 0.93 | 22.13 ± 0.7 | 20.12 ± 0.58 | 24.36 ± 0.47 | |
21 | 20.84 ± 0.46 | 19.3 ± 0.24 | 24.64 ± 0.57 | 21.44 ± 0.72 | 23.92 ± 0.14 | |
28 | 21.54 ± 1.03 | 20.09 ± 0.47 | 24.03 ± 0.54 | 22.81 ± 0.69 | 23.3 ± 0.66 | |
35 | – | – | – | – | 19.78 ± 0.29 | |
42 | – | – | – | – | 23.95 ± 0.35 | |
Female | 7 | 14.62 ± 0.30 | 14.18 ± 0.46 | 13.86 ± 0.35 | 12.61 ± 0.90 | 14.00 ± 0.82 |
14 | 15.83 ± 0.57 | 16.43 ± 0.48 | 15.15 ± 0.33 | 17.17 ± 0.34 | 16.90 ± 1.27 | |
21 | 15.77 ± 0.87 | 15.81 ± 0.33 | 15.11 ± 0.54 | 17.12 ± 0.30 | 17.63 ± 0.28 | |
28 | 16.35 ± 0.68 | 17.74 ± 0.68 | 17.22 ± 0.39 | 18.89 ± 0.52 | 19.63 ± 1.11 | |
35 | – | – | – | – | 20.69 ± 0.49 | |
42 | – | – | – | – | 18.88 ± 1.08 |
Sex | Day | Control | 250 mg/kg | 500 mg/kg | 1000 mg/kg | 1000 mg/kg reversal |
---|---|---|---|---|---|---|
Male | 7 | 28.46 ± 0.94 | 27.49 ± 0.99 | 35.71 ± 1.08 | 30.8 ± 1.15 | 36.63 ± 1.81 |
14 | 34.46 ± 1.35 | 32.46 ± 3.27 | 39.54 ± 2.68 | 36.51 ± 0.96 | 38.57 ± 2.43 | |
21 | 35.46 ± 2.50 | 30.57 ± 1.10 | 44.74 ± 0.65 | 41.69 ± 1.53 | 39.06 ± 1.14 | |
28 | 30.69 ± 1.46 | 32.74 ± 1.49 | 30.14 ± 0.55 | 42.8 ± 1.72 | 38.66 ± 1.79 | |
35 | – | – | – | – | 37.09 ± 2.27 | |
42 | – | – | – | – | 36.94 ± 1.05 | |
Female | 7 | 30.51 ± 1.14 | 25.77 ± 1.19 | 26.46 ± 2.84 | 29.29 ± 1.31 | 27.63 ± 3.13 |
14 | 29.6 ± 29.69 | 24.4 ± 28.03 | 28.8 ± 30.11 | 33.2 ± 35.54 | 28.00 ± 29.09 | |
21 | 32.00 ± 29.89 | 27.00 ± 24.17 | 27.6 ± 25.60 | 35.00 ± 34.17 | 36.2 ± 30.14 | |
28 | 32.83 ± 2.83 | 36.8 ± 2.43 | 35.94 ± 1.91 | 38.26 ± 2.20 | 37.11 ± 2.06 | |
35 | – | – | – | – | 40.31 ± 3.37 | |
42 | – | – | – | – | 27.17 ± 2.13 |
Relative organ weights
Sex | Organ | Control | Asdamarin (mg/kg, B.W) | |||
---|---|---|---|---|---|---|
250 mg/kg | 500 mg/kg | 1000 mg/kg | 1000 R mg/kg | |||
Male | Brain | 0.808 ± 0.05 | 0.795 ± 0.03 | 0.659 ± 0.006* | 0.714 ± 0.042 | 0.686 ± 0.014 |
Heart | 0.368 ± 0.03 | 0.337 ± 0.01 | 0.308 ± 0.006 | 0.326 ± 0.016 | 0.303 ± 0.004 | |
Liver | 3.613 ± 0.14 | 3.360 ± 0.13 | 3.511 ± 0.126 | 3.815 ± 0.126 | 2.456 ± 0.047 | |
Spleen | 0.486 ± 0.09 | 0.44 ± 0.02 | 0.399 ± 0.036 | 0.447 ± 0.04 | 0.392 ± 0.03 | |
Kidneys | 0.339 ± 0.01 | 0.335 ± 0.02 | 0.308 ± 0.019 | 0.341 ± 0.015 | 0.284 ± 0.009 | |
Female | Brain | 0.930 ± 0.033 | 0.858 ± 0.022 | 0.914 ± 0.028 | 0.913 ± 0.019 | 0.874 ± 0.032 |
Heart | 0.403 ± 0.026 | 0.388 ± 0.021 | 0.385 ± 0.0187 | 0.396 ± 0.007 | 0.336 ± 0.013 | |
Liver | 3.349 ± 0.331 | 3.199 ± 0.150 | 3.054 ± 0.228 | 3.150 ± 0.089 | 2.627 ± 0.084 | |
Spleen | 0.520 ± 0.061 | 0.465 ± 0.076 | 0.448 ± 0.036 | 0.523 ± 0.045 | 0.325 ± 0.026 | |
Kidneys | 0.503 ± 0.025 | 0.515 ± 0.015 | 0.505 ± 0.022 | 0.521 ± 0.008 | 0.455 ± 0.024 |
Haematology and clinical biochemistry analysis
Unit | Control | Asdamarin (mg/kg, B.W) | ||||
---|---|---|---|---|---|---|
250 | 500 | 1000 | 1000 Reversal | |||
Male | ||||||
Haemoglobin | g/dL | 16.78 ± 0.56 | 17.60 ± 0.27 | 15.40 ± 0.66 | 16.06 ± 0.56 | 16.26 ± 0.51 |
RBC | 106/μL | 9.848 ± 1.25 | 8.55 ± 0.15 | 7.72 ± 0.24 | 7.97 ± 0.3 | 7.97 ± 0.27 |
HCT | % | 43.98 ± 0.66 | 45.66 ± 0.53 | 40.40 ± 1.08 | 41.24 ± 1.84 | 41.00 ± 1.26 |
MCV | fL | 51.98 ± 1.03 | 53.54 ± 1.16 | 52.48 ± 1.33 | 51.80 ± 0.85 | 51.52 ± 0.82 |
MCH | Pg | 19.74 ± 0.39 | 20.56 ± 0.41 | 19.86 ± 0.3 | 20.12 ± 0.20 | 20.34 ± 0.32 |
MCHC | g/dL | 38.10 ± 1.06 | 38.50 ± 0.22 | 38.04 ± 1.06 | 38.96 ± 0.43 | 39.60 ± 0.35 |
Platelets | 103/μL | 270.6 ± 21.78 | 307.4 ± 16.85 | 313.0 ± 16.88 | 313.6 ± 10.16 | 311.4 ± 20.48 |
WBC | 103/μL | 22.06 ± 0.87 | 19.22 ± 3.12 | 19.46 ± 1.29 | 19.62 ± 2.76 | 20.04 ± 2.11 |
Lymphocytes | % | 90.92 ± 1.66 | 88.74 ± 0.88 | 93.84 ± 0.62 | 93.94 ± 0.76 | 90.20 ± 1.47 |
Monocytes | % | 3.18 ± 0.41 | 3.42 ± 0.19 | 2.35 ± 0.16 | 2.27 ± 0.14 | 2.97 ± 0.30 |
Neutrophils | % | 4.54 ± 1.08 | 6.38 ± 0.7 | 2.80 ± 0.41 | 2.82 ± 0.56 | 5.56 ± 1.08 |
Eosinophils | % | 1.33 ± 0.17 | 1.43 ± 0.07 | 0.99 ± 0.07 | 0.95 ± 0.06 | 1.25 ± 0.12 |
Basophils | % | 0.06 ± 0.02 | 0.06 ± 0.02 | 0.06 ± 0.02 | 0.06 ± 0.02 | 0.06 ± 0.02 |
Clotting time | Seconds | 33.0 ± 14.59 | 32.60 ± 4.49 | 39.80 ± 21.67 | 25.00 ± 4.50 | 27.40 ± 5.97 |
Female | ||||||
Haemoglobin | g/dL | 16.68 ± 0.57 | 15.48 ± 0.30 | 16.64 ± 0.466 | 15.50 ± 0.59 | 15.42 ± 0.34 |
RBC | 106/μL | 7.57 ± 0.26 | 7.67 ± 0.21 | 7.13 ± 0.24 | 6.93 ± 0.62 | 7.45 ± 0.10 |
HCT | % | 43.98 ± 1.66 | 39.22 ± 0.53 | 38.78 ± 1.03 | 36.84 ± 3.15 | 39.36 ± 0.72 |
MCV | fL | 58.14 ± 1.22 | 54.28 ± 1.18 | 56.74 ± 0.83 | 60.32 ± 1.09 | 56.90 ± 0.33 |
MCH | Pg | 22.00 ± 0.29 | 20.16 ± 0.39 | 20.48 ± 0.31 | 21.38 ± 1.59 | 20.64 ± 0.27 |
MCHC | g/dL | 37.90 ± 0.36 | 39.42 ± 0.26 | 39.74 ± 0.31 | 40.18 ± 2.81 | 39.14 ± 0.35 |
Platelets | 103/μL | 310.8 ± 40.08 | 345.2 ± 12.87 | 300.0 ± 28.68 | 338.8 ± 41.25 | 272.8 ± 18.13 |
WBC | 103/μL | 11.02 ± 1.71 | 8.28 ± 1.25 | 8.40 ± 1.38 | 9.36 ± 1.53 | 9.36 ± 1.58 |
Lymphocytes | % | 91.28 ± 1.66 | 94.30 ± 0.24 | 94.64 ± 0.79 | 93.04 ± 0.58 | 92.18 ± 1.82 |
Monocytes | % | 2.954 ± 0.52 | 2.18 ± 0.11 | 2.19 ± 0.34 | 2.016 ± 0.24 | 2.70 ± 0.52 |
Neutrophils | % | 4.50 ± 0.97 | 2.58 ± 0.12 | 3.22 ± 0.33 | 3.08 ± 0.28 | 3.96 ± 1.21 |
Eosinophils | % | 1.25 ± 0.22 | 0.92 ± 0.04 | 0.92 ± 0.15 | 0.85 ± 0.10 | 1.13 ± 0.21 |
Basophils | % | 0.06 ± 0.02 | 0.06 ± 0.02 | 0.06 ± 0.02 | 0.06 ± 0.02 | 0.06 ± 0.02 |
Clotting time | Seconds | 64.2 ± 19.90 | 33.0 ± 5.46 | 26.40 ± 3.09 | 39.00 ± 11.79 | 53.80 ± 14.61 |
Unit | Control | Asdamarin (mg/kg) | ||||
---|---|---|---|---|---|---|
250 | 500 | 1000 | 1000 Reversal | |||
Male | ||||||
ALT | IU/L | 209.2 ± 69.38 | 212.0 ± 60.64 | 146.8 ± 7.14 | 219.0 ± 46.85 | 66.0 ± 6.88 |
AST | IU/L | 296.9 ± 53.02 | 279.6 ± 43.44 | 228.6 ± 10.88 | 238.8 ± 25.25 | 208.4 ± 20.78 |
ALP | IU/L | 276.9 ± 39.06 | 246.1 ± 5.54 | 221.4 ± 29.71 | 207.2 ± 18.54 | 299.3 ± 39.60 |
Total Protein | g/dL | 6.20 ± 0.39 | 12.08 ± 3.37 | 8.0 ± 1.36 | 5.90 ± 1.33 | 8.52 ± 0.46 |
Albumin | mg/dL | 3.60 ± 0.19 | 4.58 ± 0.76 | 5.24 ± 1.37 | 6.62 ± 1.59 | 4.06 ± 0.25 |
Glucose | mg/dL | 115.7 ± 6.16 | 135.1 ± 7.95 | 92.22 ± 16.19 | 131.3 ± 19.92 | 114.9 ± 10.15 |
Total bilirubin | mg/dL | 0.24 ± 0.24 | 0.24 ± 0.02 | 0.26 ± 0.04 | 0.74 ± 0.31 | 0.26 ± 0.024 |
Direct bilirubin | mg/dL | 0.12 ± 0.02 | 0.10 ± 0.03 | 0.160 ± 0.04 | 0.14 ± 0.05 | 0.120 ± 0.02 |
Urea | mg/dL | 37.43 ± 5.72 | 35.17 ± 3.32 | 33.83 ± 3.83 | 48.17 ± 4.30 | 54.67 ± 6.33 |
Creatinine | mg/dL | 0.64 ± 0.07 | 0.79 ± 0.31 | 2.18 ± 1.14 | 1.74 ± 0.91 | 0.84 ± 0.05 |
Cholesterol | mg/dL | 53.03 ± 7.22 | 57.13 ± 5.34 | 63.78 ± 2.80 | 58.57 ± 21.28 | 78.85 ± 6.40 |
Triglycerides | mg/dL | 52.57 ± 14.57 | 51.34 ± 10.32 | 66.43 ± 9.29 | 58.75 ± 20.85 | 70.86 ± 6.37 |
HDL | mg/dL | 43.08 ± 4.87 | 47.99 ± 3.80 | 50.11 ± 1.60 | 53.53 ± 6.99 | 68.72 ± 5.94** |
Calcium | mg/dL | 9.87 ± 0.78 | 19.37 ± 9.54 | 12.60 ± 3.15 | 14.56 ± 4.40 | 10.96 ± 0.55 |
Phosphorous | mg/dL | 17.32 ± 6.07 | 24.04 ± 6.85 | 22.38 ± 3.1 | 26.08 ± 11.58 | 21.34 ± 16.60 |
Female | ||||||
ALT | IU/L | 74.40 ± 4.88 | 105.0 ± 15.44 | 101.4 ± 10.46 | 108.6 ± 16.59 | 52.2 ± 7.14 |
AST | IU/L | 170.6 ± 7.69 | 180.4 ± 15.46 | 178.5 ± 17.91 | 189.0 ± 23.67 | 175.5 ± 9.74 |
ALP | IU/L | 160.0 ± 17.89 | 190.5 ± 31.15 | 142.7 ± 6.46 | 184.6 ± 34.12 | 165.4 ± 18.7 |
Total Protein | g/dL | 13.90 ± 1.24 | 14.1 ± 1.56 | 11.48 ± 1.00 | 11.84 ± 1.59 | 10.58 ± 1.14 |
Albumin | mg/dL | 4.08 ± 0.08 | 3.86 ± 0.09 | 3.720 ± 0.31 | 3.82 ± 0.198 | 3.66 ± 0.19 |
Glucose | mg/dL | 107.7 ± 9.17 | 117.8 ± 22.54 | 121.1 ± 11.32 | 110.1 ± 34.12 | 109.9 ± 6.27 |
Total bilirubin | mg/dL | 0.28 ± 0.04 | 0.34 ± 0.14 | 0.36 ± 0.09 | 0.26 ± 0.07 | 0.32 ± 0.037 |
Direct bilirubin | mg/dL | 0.16 ± 0.02 | 0.18 ± 0.08 | 0.24 ± 0.05 | 0.14 ± 0.02 | 0.16 ± 0.02 |
Urea | mg/dL | 123.2 ± 13.82 | 107.8 ± 17.75 | 150.7 ± 36.99 | 130.7 ± 12.54 | 51.49 ± 3.86 |
Creatinine | mg/dL | 0.43 ± 0.04 | 1.09 ± 0.66 | 1.83 ± 1.21 | 1.04 ± 0.17 | 0.69 ± 0.1 |
Cholesterol | mg/dL | 69.58 ± 8.39 | 55.86 ± 4.96 | 53.24 ± 6.20 | 63.03 ± 8.54 | 61.76 ± 3.76 |
Triglycerides | mg/dL | 65.15 ± 12.15 | 44.65 ± 13.84 | 53.12 ± 10.79 | 44.05 ± 23.35 | 101.7 ± 29.26 |
HDL | mg/dL | 64.70 ± 5.65 | 60.44 ± 5.52 | 62.44 ± 6.70 | 68.13 ± 3.76 | 74.76 ± 3.92 |
Calcium | mg/dL | 9.41 ± 0.19 | 8.44 ± 0.42 | 9.54 ± 0.90 | 7.35 ± 2.65 | 9.33 ± 0.13 |
Phosphorous | mg/dL | 23.02 ± 2.88 | 14.90 ± 5.17 | 13.28 ± 5.31 | 22.70 ± 6.80 | 24.42 ± 4.2 |