Toxicological study of the hepatotherapeutic herbal formula, Chunggan extract, in beagle dogs

Table 1 Summary for clinical observation and histological examination

CGX (mg/kg per day)	0	100	200	400
Mortality	-	-	-	-
Clinical signs	NAD	NAD	NAD	NAD
Anorexia	-	-	-	-
Soft feces	-	-	-	-
Food intake	NAD	NAD	NAD	NAD
Ophthalmologic findings	NAD	NAD	NAD	NAD
Relative organ weight	NS	NS	NS	NS
Necropsy findings	NAD	NAD	NAD	NAD
Histopathological findings	Rarely in some samples	Rarely in some samples
Liver	Focal necrosis	Subcutaneous necrosis
Lung	Yellow pigmentation	Yellow pigmentation
Kidney	Glomerular hyperemia	Glomerular hyperemia
Spleen	White pulp atrophy	White pulp atrophy
Stomach	Helicobacter	Helicobacter

Three male and three female beagle dogs in each group were fed CGX, and the clinical symptoms including mortality were monitored for 4 wk. At the end of the experiment, ophthalmologic, necropsy-based, and histopathological examinations were performed. NAD: No abnormality detected; NS: Not significant; -: Absent.

Table 2 Haematological analysis after administration of Chunggan extract for 4 wk

Number of dogs	Male (12)				Female (12)
CGX (mg/kg•d)	0	100	200	400	0	100	200	400
Erythrocyte (M/UL)	6.4 ± 0.6	6.80 ± 0.4	6.56 ± 0.4	6.70 ± 0.1	6.22 ± 0.5	6.70 ± 0.5	6.77 ± 0.5	6.59 ± 0.2
Hemoglobin (g/dL)	18.6 ± 2.1	17.6 ± 0.4	18.2 ± 1.0	18.1 ± 1.3	16.5 ± 1.7	17.5 ± 1.8	17.8 ± 0.4	17.7 ± 0.1
Hematocrit (%)	41.3 ± 4.1	42.8 ± 1.8	42.8 ± 2.2	42.2 ± 1.0	39.2 ± 2.8	40.1 ± 2.1	43.3 ± 3.9	41.6 ± 0.9
MCV (fL)	64.1 ± 0.3	63.1 ± 2.4	65.4 ± 2.8	62.9 ± 1.0	63.1 ± 0.1	60.1 ± 4.1	63.9 ± 1.4	63.1 ± 1.9
MCH (pg)	28.9 ± 1.1	26.0 ± 1.4	27.8 ± 2.3	27.0 ± 1.7	26.5 ± 1.2	26.1 ± 2.7	26.4 ± 2.4	26.8 ± 0.7
MCHC (g/dL)	45.2 ± 1.5	41.7 ± 0.6a	42.4 ± 2.2	42.9 ± 2.2	42.1 ± 2.2	43.5 ± 2.5	41.3 ± 4.6	42.6 ± 0.7
RDW (%)	15.1 ± 0.1	15.9 ± 0.3	15.3 ± 0.4	15.9 ± 0.3	15.7 ± 0.1	15.9 ± 0.6	15.7 ± 0.5	15.1 ± 0.1
Reticulocytes (%)	0.30 ± 0.1	0.23 ± 0.1	0.37 ± 0.2	0.43 ± 0.2	0.77 ± 0.2	0.50 ± 0.4	0.53 ± 0.6	0.50 ± 0.2
Platelets (k/UL)	349 ± 13	320 ± 125	334 ± 50	344 ± 46	347 ± 94	333 ± 90	239 ± 87	245 ± 18
MPV (fL)	12.8 ± 0.3	15.1 ± 1.2	14.6 ± 2.2	14.0 ± 1.3	13.4 ± 1.6	12.8 ± 1.6	16.4 ± 4.2	15.0 ± 4.7
PT (s)	6.73 ± 0.2	7.20 ± 0.6	6.63 ± 0.3	6.77 ± 0.2	6.73 ± 0.3	7.00 ± 0.4	6.77 ± 0.1	6.93 ± 0.5
aPTT (s)	14.2 ± 0.5	19.3 ± 5.2	15.4 ± 0.7	15.2 ± 0.9	15.7 ± 0.2	15.4 ± 0.9	16.1 ± 2.6	16.5 ± 0.7
Leukocytes (k/UL)	9.86 ± 1.2	9.51 ± 1.3	8.56 ± 1.3	11.4 ± 1.4	9.64 ± 1.3	10.6 ± 0.2	11.8 ± 3.8	8.9 ± 1.6
Neutrophil (%)	61.0 ± 10	59.8 ± 15	65.7 ± 14	66.9 ± 10	57.0 ± 13	60.9 ± 14	49.2 ± 2.3	62.8 ± 13
Lymphocyte (%)	19.5 ± 4.1	23.7 ± 4.2	21.4 ± 4.7	21.8 ± 2.6	28.2 ± 5.2	26.7 ± 8.5	35.5 ± 13	27.1 ± 7.9
Monocytes (%)	7.5 ± 2.0	8.0 ± 3.2	6.9 ± 1.2	5.3 ± 0.9	7.2 ± 1.0	7.6 ± 5.7	10.4 ± 5.1	7.8 ± 2.2
Eosinophil (%)	11.6 ± 9.1	8.41 ± 4.2	5.96 ± 5.8	5.70 ± 1.7	7.47 ± 11	4.25 ± 1.9	4.15 ± 1.7	2.70 ± 2.4
Basophil (%)	0.30 ± 0.3	0.11 ± 0.1	0.12 ± 0.3	0.26 ± 0.2	0.31 ± 0.6	0.13 ± 0.1	0.34 ± 0.5	0.11 ± 0.1

After administration of Chunggan extract (CGX) for 4 wk, haematology was analysed to compare CGX-treated groups to the control group. MCV: Mean corpuscular volume; MCH: Mean corpuscular haemoglobin; MCHC: Mean corpuscular haemoglobin concentration; RDW: Red cell distribution width; MPV: Mean platelet volume; PT: Prothrombin time; APPT: Activated partial thromboplastin time. aindicates a significant difference at a level of P < 0.05.

Table 3 Serum chemistry analysis after administration of Chunggan extract for 4 wk

Number of dogs	Male (12)				Female (12)
CGX (mg/kg per day)	0	100	200	400	0	100	200	400
AST (IU/L)	37.0 ± 3.4	36.3 ± 2.0	40.3 ± 14.2	41.3 ± 8.3	40.6 ± 8.5	34.3 ± 5.7	37.0 ± 4.3	40.0 ± 9.5
ALT (IU/L)	57.6 ± 7.3	48.6 ± 8.1	49.3 ± 29.7	65.6 ± 24.0	38.0 ± 7.0	46.6 ± 16.2	44.0 ± 1.7	33.6 ± 9.0
ALP (IU/L)	328 ± 46	299 ± 102	390 ± 221	238 ± 74	271 ± 104	391 ± 93	377 ± 159	174 ± 43
BUN (mg/dL)	18.2 ± 1.3	20.1 ± 3.1	22.8 ± 3.6	19.3 ± 3.5	13.4 ± 1.9	17.6 ± 2.6	13.9 ± 3.9	24.4 ± 4.8a
Creatinine (mg/dL)	1.05 ± 0.1	1.20 ± 0.1	1.23 ± 0.1	1.18 ± 0.1	1.03 ± 0.2	1.15 ± 0.1	1.09 ± 0.1	1.11 ± 0.1
Glucose (mg/dL)	99.0 ± 15.5	115.6 ± 5.1	112.3 ± 11.9	110.7 ± 4.2	114 ± 14	121 ± 10.2	117 ± 5.6	116 ± 26.1
Total chol. (mg/dL)	252 ± 30	223 ± 34	260 ± 25	217 ± 51	299 ± 73	296 ± 34	263 ± 24	261 ± 58
Total bilirubin (mg/dL)	0.23 ± 0.1	0.27 ± 0.1	0.23 ± 0.1	0.30 ± 0.1	0.30 ± 0.1	0.30 ± 0.0	0.30 ± 0.1	0.33 ± 0.1
Total protein (g/dL)	7.83 ± 0.2	7.37 ± 0.2	7.33 ± 0.2	7.37 ± 0.3	7.60 ± 0.3	7.47 ± 0.6	7.40 ± 0.4	7.53 ± 0.2
Albumin (g/dL)	4.73 ± 0.3	4.33 ± 0.2	4.47 ± 0.1	4.60 ± 0.4	4.77 ± 0.3	4.50 ± 0.3	4.63 ± 0.3	4.57 ± 0.2
AG ratio	1.53 ± 0.2	1.43 ± 0.2	1.60 ± 0.2	1.67 ± 0.3	1.70 ± 0.1	1.50 ± 0.1	1.70 ± 0.1	1.57 ± 0.1
C.phosphokinase (IU/L)	133 ± 15	130 ± 39	171 ± 89	157 ± 48	199 ± 30	116 ± 24	155 ± 37	144 ± 23
Triglyceride (mg/dL)	25.0 ± 3.0	35.6 ± 24.8	30.0 ± 3.6	287 ± 7.2	36.0 ± 16.6	28.4 ± 9.5	36.0 ± 5.2	47.3 ± 17.1
Calcium (mg/dL)	14.8 ± 0.5	14.5 ± 0.5	14.6 ± 0.3	14.4 ± 0.2	14.5 ± 0.5	14.7 ± 0.9	14.1 ± 0.4	14.6 ± 0.7
Inorganic pho. (mg/dL)	3.33 ± 1.1	4.43 ± 0.3	4.23 ± 0.3	4.43 ± 0.6	3.80 ± 0.5	3.90 ± 0.6	4.03 ± 0.8	3.63 ± 0.3
LDH (IU/L)	105 ± 45.7	132 ± 73.5	91.7 ± 32.8	106 ± 60.3	80.0 ± 11.5	68.3 ± 9.7	146 ± 60.7	146 ± 126.1
GGT (IU/L)	4.63 ± 0.3	3.93 ± 1.3	4.03 ± 0.4	4.37 ± 1.3	4.93 ± 1.0	5.13 ± 0.4	4.57 ± 1.0	5.53 ± 0.5
Sodium (mmol/dL)	148 ± 2.0	146 ± 1.1	144 ± 2.1	144 ± 0.6	146 ± 1.2	148 ± 1.00	147 ± 2.0	147 ± 0.4
Potassium (mmol/dL)	4.21 ± 0.1	4.32 ± 0.1	4.31 ± 0.2	4.18 ± 0.2	4.08 ± 0.23	3.95 ± 0.2	4.24 ± 0.3	4.42 ± 0.4
Chloride (mmol/dL)	116 ± 1.1	115 ± 2.5	115 ± 2.3	116 ± 0.6	117 ± 1.5	114 ± 1.5	114 ± 3.2	114 ± 1.5

After administration of Chunggan extract (CGX) for 4 wk, serum chemistry was analysed to compare CGX-treated groups to the control group. AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; BUN: Blood urea nitrogen; AG ratio: Albumin globulin ratio; LDH: Lactate dehydrogenase; GGT: Gamma glutamyl transferase.

^aP < 0.05 among BUN in female grops treated with 0 mg, 100 mg, 200 mg and 400 mg CGX.