Safety of Curcuma aromatica oil gelatin microspheres administered via hepatic artery

Table 1 Deaths of the rats after administration of CAO-GMS

Group	Number of rats	Dosage (mg/kg)	Number of dead rats	Mortality (%)	Peak time of death occurrence (h)
CAO-GMS-1	10	5	0	0	-
CAO-GMS-2	12	10	4	33.33	24-48
CAO-GMS-3	14	20	8	57.14	24-48
CAO-GMS-4	12	40	12	100	< 24
GMS	10	40	7	71.42	24-48
Blank control	8	3.51	0	0	-
CAO	8	3.2	0	0	-

¹Measured in mL/kg.

Table 2 Changes in biochemical indices of the dying rats receiving CAO-GMS (mean ± SD)

Group	Nurmber of rats	ALT (U/L)	AST (U/L)	T-BiL (mmol/L)	D-BiL (μmol/L)	BCr (μmol/L)	BUN (mmol/L)
CAO-GMS-1	0	-	-	-	-	-	-
CAO-GMS-2	4	200 ± 54b	805 ± 533b	12.0 ± 5b	46.0 ± 90b	50.0 ± 34b	20.0 ± 12a
CAO-GMS-3	8	186 ± 89b	700 ± 522b	12.4 ± 8.6b	59.0 ± 88b	49.0 ± 43b	20.0 ± 14a
CAO-GMS-4	12	241 ± 289b	715 ± 614b	15.0 ± 19b	78.0 ± 162b	58.0 ± 43b	22.0 ± 13a
GMS	7	232 ± 168b	685 ± 503b	13.8 ± 9.6b	54.0 ± 126b	52.0 ± 36b	20.0 ± 13a
Blank control	0	38 ± 11	278 ± 114	4.5 ± 1.3	3.2 ± 1.6	38.7 ± 3.5	8.6 ± 11.8
CAO	0	-	-	-	-	-	-

^aP < 0.05;

^bP < 0.01 vs blank control.

Table 3 Changes in biochemical indices of survived rats receiving CAO-GMS (mean ± SD)

Group	Nurmber of rats	ALT (U/L)	AST (U/L)	T-BiL (mmol/L)	D-BiL (μmmol/L)	BCr (μmmol/L)	BUN (mmol/L)
CAO-GMS-1	10	37.7 ± 5.5	310 ± 96	5.4 ± 1.4	3.8 ± 1.4	40.3 ± 5.2	8.42 ± 0.69
CAO-GMS-2	8	39.2 ± 7.7	301 ± 74	5.2 ± 1.7	3.6 ± 1.8	41.8 ± 9.3	10.00 ± 2.2
CAO-GMS-3	6	39.0 ± 10	314 ± 59	7.4 ± 4.7	4.5 ± 2.9	39.0 ± 13	9.20 ± 2.9
CAO-GMS-4	0	-	-	-	-	-	-
GMS	3	46.0 ± 6.5	265 ± 114	4.0 ± 1.5	2.9 ± 1.6	35.0 ± 1.4	7.60 ± 1.4
Blank control	8	38.0 ± 11	278 ± 114	4.5 ± 1.3	3.2 ± 1.6	38.7 ± 3.5	8.60 ± 1.8
CAO	8	36.0 ± 7	307 ± 84	4.8 ± 1.9	3.2 ± 1.7	39.4 ± 2.4	8.00 ± 1.6

Table 4 Changes in respiration, rates blood pressure and ECG in dogs at different time points after CAO (6.4 μL/kg) interventional therapy (mean ± SD)

Time point	Nurmber of rats	Respiration frequency (breath/min)	Heart rate (beat/min)	Blood pressure (mmHg)
				Systolic	Diastolic
Preoperation	4	17.0 ± 10.2	198.5 ± 38.4	147.8 ± 8.2	116.0 ± 11.5
30 min postoperative	4	15.0 ± 7.0	193.5 ± 36.1	141.5 ± 8.2	114.8 ± 9.7
60 min postoperative	4	16.0 ± 8.5	189.3 ± 27.1	140.5 ± 8.9	115.8 ± 9.3
120 min postoperative	4	17.8 ± 9.5	190.5 ± 23.6	141.5 ± 3.3	117.0 ± 5.0
180 min postoperative	4	13.8 ± 6.0	189.0 ± 28.4	143.5 ± 5.8	119.0 ± 6.3

Table 5 Changes in respiration, blood pressure and ECG in dogs at different time points after CAO-GMS interventional therapy (mean ± SD)

Time point	Dosage	Number of rats	Respiration frequency (/min)	Heart rate (/min)	Blood pressure (mmHg)
					Systolic	Diastolic
Preoperation	0.10	6	19.0 ± 5.2	219.0 ± 22.7	142.5 ± 9.0	112.7 ± 9.1
	0.03	6	13.5 ± 4.9	196.0 ± 28.5	144.7 ± 12.2	116.2 ± 9.8
30 min postoperative	0.10	6	20.5 ± 6.7	214.7 ± 19.1	142.7 ± 7.3	113.0 ± 8.6
	0.03	6	14.0 ± 4.9	198.3 ± 17.7	146.3 ± 11.3	118.8 ± 12.6
60 min postoperative	0.10	6	19.7 ± 7.7	211.5 ± 18.7	142.3 ± 6.4	113.5 ± 8.1
	0.03	6	12.3 ± 3.4	194.0 ± 16.6	144.0 ± 10.7	119.2 ± 13.6
120 min postoperative	0.10	6	19.5 ± 7.8	211.7 ± 25.0	142.3 ± 10.0	114.0 ± 10.7
	0.03	6	15.3 ± 5.5	193.7 ± 20.2	145.0 ± 9.1	118.8 ± 9.2
180 min postoperative	0.10	6	20.3 ± 8.9	209.3 ± 30.2	141.5 ± 12.3	114.5 ± 13.1
	0.03	6	16.8 ± 6.8	193.7 ± 21.6	143.8 ± 9.5	119.2 ± 9.5

Table 6 Changes in respiration, blood pressure and ECG in dogs at different time points after GMS (0.1 g) interventional therapy (mean ± SD)

Time point	Number of rats	Respiration frequency (/min)	Heart rate (/min)	Blood pressure (mmHg)
				Systolic	Diastolic
Preoperation	5	20.4 ± 6.2	186.6 ± 28.3	133.4 ± 16.0	109.4 ± 16.9
30 min postoperative	5	18.0 ± 5.8	178.2 ± 28.6	139.8 ± 20.0	116.0 ± 14.9
60 min postoperative	5	18.2 ± 5.8	179.0 ± 29.2	143.8 ± 20.7	117.2 ± 17.4
120 min postoperative	5	17.4 ± 3.8	183.8 ± 34.1	146.0 ± 17.7	121.0 ± 18.9
180 min postoperative	5	18.0 ± 4.1	180.0 ± 37.5	142.6 ± 20.0	116.8 ± 19.7