TABLE 3.

Clinical Chemistry Parameters of Male Wistar Rats after Repeated Administration of BI-2, BI-3, Gentamicin, or IMM125 for 1, 3, and 12 (urine) or 14 (serum) Days

	Days of treatment	BI-2			BI-3			Gentamicin			IMM125
		0 mg/kg	2.5 mg/kg	15 mg/kg	0 mg/kg	100 mg/kg	1000 mg/kg	0 mg/kg	25 mg/kg	75 mg/kg	0 mg/kg	30 mg/kg	100 mg/kg
Urine
Creatinine (mg/16 h)	1	4.3	3.9	4.4 ± 0.8	7.9 ± 1.3	8.5 ± 0.8	6.8 ± 1.6	2.4 ± 0.2	2.6 ± 0.3	2.3 ± 0.1	4.3 ± 1.1	4.7 ± 0.7	5.3 ± 0.7
	3	5.1 ± 0.5	4.0 ± 0.0*	3.7 ± 0.1*	8.1 ± 1.5	8.9 ± 1.3	6.3 ± 1.1	2.7 ± 0.3	2.7 ± 0.3	2.6 ± 0.3	4.8 ± 1.4	5.5 ± 0.8	6.0 ± 1.1
	12	5.6 ± 0.6	4.8 ± 0.7	4.5 ± 0.3	7.7 ± 1.2	7.7 ± 2.0	5.5 ± 1.8	3.9 ± 0.7	3.8 ± 0.6	3.8 ± 0.3	6.1 ± 1.0	6.9 ± 1.2	7.0 ± 0.6
Protein (mg/mg creatinine)	1	Not determined			0.5 ± 0.1	0.5 ± 0.1	0.7 ± 0.6	1.0 ± 0.1	0.9 ± 0.2	1.1 ± 0.3	0.1 ± 0.1	0.5 ± 0.4	0.6 ± 0.5
	3	Not determined			0.5 ± 0.1	0.7 ± 0.2	1.1 ± 0.9	1.0 ± 0.2	1.0 ± 0.3	1.3 ± 0.3	0.3 ± 0.2	0.3 ± 0.3	0.4 ± 0.7
	12	Not determined			0.7 ± 0.6	1.1 ± 0.9	0.6 ± 0.4	1.4 ± 0.3	2.3 ± 0.7	2.7 ± 0.6*	0.4 ± 0.2	0.3 ± 0.1	0.5 ± 0.2
Serum
Creatinine (mg/dl)	1	0.43 ± 0.13	0.42 ± 0.05	0.37 ± 0.06	0.51 ± 0.03	0.46 ± 0.03	0.47 ± 0.03	0.17 ± 0.02	0.16 ± 0.02	0.16 ± 0.02	0.28 ± 0.05	0.29 ± 0.07	0.22 ± 0.02
	3	0.41 ± 0.04	0.44 ± 0.05	0.43 ± 0.07	0.52 ± 0.04	0.45 ± 0.04*	0.48 ± 0.04	0.19 ± 0.01	0.19 ± 0.04	0.21 ± 0.02	0.25 ± 0.04	0.27 ± 0.05	0.30 ± 0.08
	14	0.46 ± 0.07	0.41 ± 0.05	0.45 ± 0.04	0.52 ± 0.07	0.53 ± 0.05	0.65 ± 0.32	0.21 ± 0.03	0.22 ± 0.03	0.26 ± 0.02*	0.32 ± 0.02	0.32 ± 0.04	0.35 ± 0.04
BUN (mg/dl)	1	25 ± 3	27 ± 2	25 ± 2	49 ± 6	53 ± 17	46 ± 9	41 ± 4	39 ± 5	43 ± 6	13 ± 3	13 ± 4	13 ± 3
	3	25 ± 4	28 ± 3	31 ± 7	50 ± 7	48 ± 7	67 ± 19	47 ± 7	46 ± 7	48 ± 7	14 ± 2	14 ± 3	15 ± 4
	14	26 ± 2	26 ± 1	29 ± 4	45 ± 6	60 ± 6	110 ± 72	38 ± 6	41 ± 5	48 ± 4*	15 ± 1	17 ± 3	17 ± 3
GGT (U/l)	1	0.40 ± 0.14	1.95 ± 2.19	0.18 ± 0.40	0.00 ± 0.00	0.01 ± 0.03	1.75 ± 1.38**	< LOD	< LOD	< LOD	1.86 ± 1.90	1.02 ± 1.42	1.54 ± 2.21
	3	1.00 ± 0.85	0.88 ± 0.29	0.35 ± 0.21	0.00 ± 0.00	0.00 ± 0.00	1.60 ± 2.44	< LOD	< LOD	< LOD	1.60 ± 3.58	2.54 ± 3.69	2.20 ± 3.73
	14	1.15 ± 0.21	0.04 ± 0.09	0.62 ± 0.30	0.00 ± 0.00	0.00 ± 0.00	1.65 ± 1.31**	< LOD	< LOD	< LOD	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00
Total protein (g/l)	1	55 ± 2	54 ± 4	54 ± 2	59 ± 1	58 ± 2	61 ± 2	54 ± 2	54 ± 2	54 ± 1	61 ± 1	58 ± 2*	56 ± 2**
	3	55 ± 1	55 ± 1	53 ± 2	59 ± 1	58 ± 3	56 ± 3	56 ± 2	56 ± 1	57 ± 0	64 ± 2	59 ± 3*	52 ± 3***
	14	56 ± 3	55 ± 2	52 ± 2*	58 ± 2	55 ± 2	45 ± 6***	54 ± 1	55 ± 2	55 ± 3	64 ± 2	58 ± 2***	53 ± 1***
AST (U/l)	1	53 ± 12	61 ± 32	60 ± 12	193 ± 37	167 ± 38	298 ± 195	94 ± 18	93 ± 7	102 ± 12	132 ± 10	107 ± 13*	80 ± 17***
	3	66 ± 14	75 ± 40	62 ± 8	190 ± 25	172 ± 22	215 ± 43	94 ± 10	91 ± 11	87 ± 15	108 ± 15	90 ± 10	69 ± 26*
	14	62 ± 20	65 ± 9	62 ± 6	157 ± 19	151 ± 27	144 ± 40	89 ± 16	88 ± 19	97 ± 17	138 ± 22	95 ± 7**	72 ± 9***
ALP (U/l)	1	99 ± 21	98 ± 10	104 ± 25	182 ± 25	149 ± 32	513 ± 289*	577 ± 129	536 ± 105	592 ± 156	213 ± 49.3	228 ± 61.8	191 ± 26
	3	120 ± 30	87 ± 8*	89 ± 10*	197 ± 47	177 ± 36	425 ± 77***	712 ± 179	666 ± 241	561 ± 169	245 ± 69.1	155 ± 27.1*	123 ± 12**
	14	86 ± 17	87 ± 25	57 ± 5	114 ± 11	116 ± 13	262 ± 90**	510 ± 120	455 ± 94	398 ± 131	176 ± 20.5	116 ± 24.9**	95 ± 24***
ALT (U/l)	1	26 ± 4	28 ± 8	27 ± 6	31 ± 5	28 ± 14	169 ± 185	25 ± 4	24 ± 5	23 ± 1	57 ± 9	49 ± 6	33 ± 12**
	3	29 ± 6	45 ± 41	26 ± 7	24 ± 4	22 ± 2	43 ± 14**	24 ± 4	21 ± 2	22 ± 4	54 ± 11	22 ± 9***	22 ± 6***
	14	34 ± 15	30 ± 6	27 ± 2	24 ± 4	28 ± 10	24 ± 4	26 ± 5	24 ± 2	31 ± 10	52 ± 7	46 ± 8	34 ± 8**
Bilirubin (mg/dl)	1	0.10 ± 0.02	0.09 ± 0.05	0.09 ± 0.02	Not determined			0.08 ± 0.02	0.08 ± 0.02	0.08 ± 0.01	0.07 ± 0.02	0.09 ± 0.02	0.17 ± 0.05**
	3	0.11 ± 0.04	0.11 ± 0.03	0.11 ± 0.01	Not determined			0.08 ± 0.01	0.07 ± 0.01	0.09 ± 0.01	0.09 ± 0.03	0.14 ± 0.03	0.45 ± 0.10***
	14	0.07 ± 0.03	0.04 ± 0.02	0.06 ± 0.02	Not determined			0.06 ± 0.02	0.08 ± 0.02	0.09 ± 0.01*	0.10 ± 0.03	0.17 ± 0.02*	0.28 ± 0.07***
Glucose (mg/dl)	1	175 ± 14	188 ± 9	180 ± 29	147 ± 11	132 ± 23	152 ± 20	123 ± 9	119 ± 14	122 ± 13	95 ± 16	114 ± 12	120 ± 23
	3	154 ± 9	176 ± 17*	169 ± 13	144 ± 20	143 ± 8	122 ± 6*	138 ± 22	126 ± 16	132 ± 12	74 ± 4	84 ± 9	101 ± 14**
	14	171 ± 35	191 ± 21	192 ± 14	148 ± 14	163 ± 4	128 ± 47	123 ± 25	117 ± 12	130 ± 11	80 ± 14	92 ± 15	111 ± 8**

Note. Data are presented as mean ± SD (n = 5). Statistical analysis was performed by ANOVA and Dunnett’s post hoc test; LOD, limit of detection.

*p < 0.05, **p < 0.01, and ***p < 0.001.