Acute and sub-chronic toxicity study of recombinant bovine interferon alpha in rodents

Yu, Hai-Yang; Gao, Dong-Mei; Zhou, Wei; Xia, Bing-Bing; He, Zhi-Yuan; Wu, Bo; Jiang, Min-Zhi; Wang, Ming-Li; Zhao, Jun

doi:10.2478/jvetres-2021-0023

Figures & Tables

Effects of rBoIFN-α on feed intake of male (A) and female (B) rats in sub-chronic toxicity test

Effects of rBoIFN-α on weight gain of male (A) and female (B) rats in sub-chronic toxicity test

Effects of rBoIFN-α on the morphology of liver, kidney and spleen in Sprague Dawley rats (HE staining, ×200)

Effects of rBoIFN-α on blood biochemical indexes in Sprague Dawley rats in the sub-chronic toxicity test

Time	Index	Gender	High-dose group	Middle-dose group	Low-dose group	Control group
Day 31	ALT (U/L)	M	51.10 ± 11.03	54.10 ± 7.19	46.80 ± 5.87	51.40 ± 21.00

		F	40.80 ± 7.07	43.30 ± 5.08	43.60 ± 7.98	36.00 ± 11.90

	AST (U/L)	M	194.70 ± 31.81	190.20 ± 54.94	175.70 ± 11.80	197.30 ± 44.16

		F	203.70 ± 50.69	182.80 ± 27.34	198.20 ± 29.10	188.20 ± 28.74

	BUN (mmol/L)	M	3.48 ± 0.34	4.11 ± 0.84	3.56 ± 0.44	3.55 ± 0.72

		F	5.00 ± 082	5.00 ± 0.65	5.30 ± 0.33	5.91 ± 1.10

	CREAT (μmol/L)	M	29.10 ± 3.11	29.70 ± 5.63	27.50 ± 3.36	30.30 ± 1.67

		F	32.70 ± 3.42	34.10 ± 4.92	33.20 ± 4.83	37.10 ± 3.77

	GLU (mmol/L)	M	3.74 ± 1.34	4.02 ± 0.85	4.41 ± 0.30	4.55 ± 1.58

		F	2.56 ± 0.77	2.47 ± 0.24	2.90 ± 0.49	2.70 ± 0.44

	TP (g/L)	M	56.84 ± 1.79	55.60 ± 3.66	56.15 ± 3.89	57.10 ± 1.80

		F	61.60 ± 2.33	59.72 ± 4.11	60.70 ± 3.26	60.16 ± 3.54

	ALB (g/L)	M	42.00 ± 1.07	41.88 ± 2.99	41.58 ± 2.20	41.30 ± 0.48

		F	47.01 ± 1.06	45.92 ± 2.80	45.58 ± 2.13	44.44 ± 2.25

	CHO (mmol/L)	M	2.03 ± 0.23	2.02 ± 0.14	2.11 ± 0.20	1.81 ± 0.35

		F	1.88 ± 0.36	2.00 ± 0.10	1.70 ± 0.35	1.70 ± 0.30

	TG (mmol/L)	M	0.74 ± 0.26	0.81 ± 0.09	1.01 ± 0.14	0.64 ± 0.31

		F	0.85 ± 0.29	0.79 ± 0.12	0.69 ± 0.05	0.68 ± 0.19

Day 38	ALT (U/L)	M	49.20 ± 2.30	56.20 ± 3.97	65.80 ± 15.98	60.20 ± 15.47

		F	38.50 ± 6.43	40.20 ± 5.64	42.00 ± 9.88	42.70 ± 5.17

	AST (U/L)	M	125.30 ± 13.07	120.20 ± 12.74	153.70 ± 28.60	143.00 ± 18.15

		F	124.10 ± 24.77	121.00 ± 17.03	125.50 ± 13.10	132.40 ± 13.85

	BUN (mmol/L)	M	4.73 ± 0.93	5.01 ± 0.79	4.69 ± 1.06	5.10 ± 0.95

		F	6.00 ± 0.32	5.77 ± 0.97	6.48 ± 0.36	5.96 ± 0.66

	CREAT (μmol/L)	M	29.30 ± 3.91	33.10 ± 6.95	29.00 ± 4.04	31.30 ± 3.91

		F	38.70 ± 4.02	38.50 ± 3.65	39.20 ± 3.65	34.90 ± 2.74

	GLU (mmol/L)	M	6.40 ± 0.71	6.11 ± 0.20	5.32 ± 0.79*	7.10 ± 1.62

		F	4.17 ± 0.74	4.70 ± 0.59	5.11 ± 0.51	4.71 ± 0.70

	TP (g/L)	M	57.24 ± 2.17	58.60 ± 2.46	57.16 ± 0.82	56.86 ± 1.95

		F	62.44 ± 2.64	61.30 ± 4.50	63.64 ± 1.34	63.02 ± 1.77

	ALB (g/L)	M	57.24 ± 2.17	58.50 ± 2.46	57.26 ± 0.82	57.00 ± 1.95

		F	31.70 ± 1.55	31.80 ± 2.21	32.20 ± 2.01	32.20 ± 0.79

	CHO (mmol/L)	M	1.80 ± 0.33	1.91 ± 0.05	1.63 ± 0.14	1.80 ± 0.34

		F	1.80 ± 0.18	1.62 ± 0.25	1.63 ± 0.10	1.77 ± 0.20

	TG (mmol/L)	M	0.90 ± 0.38	1.05 ± 0.52	1.02 ± 0.21	1.18 ± 0.13

		F	0.91 ± 0.02	0.86 ± 0.30	0.92 ± 0.06	1.11 ± 0.26

Effects of rBoIFN-α on haematological indexes in Sprague Dawley rats in the sub-chronic toxicity test

Time	Index	Gender	High-dose group	Middle-dose group	Low-dose group	Control group
Day 31	HGB (g/L)	M	151.30 ± 4.16	149.00 ± 6.48	147.90 ± 4.64	146.00 ± 0.11
		F	144.10 ± 7.98	142.10 ± 8.41	142.90 ± 12.65	147.50 ± 5.37
	RBC (× 10¹²/L)	M	7.72 ± 0.16	7.65 ± 0.23	7.78 ± 0.33	7.63 ± 0.13
		F	7.63 ± 0.39	7.49 ± 0.35	7.59 ± 0.52	7.64 ± 0.37
	WBC (× 10⁹/L)	M	14.45 ± 1.29	13.35 ± 2.26*	15.07 ± 2.66	16.23 ± 1.09
		F	8.54 ± 1.38	10.79 ± 1.64	8.90 ± 2.31	10.11 ± 1.38
	NE (× 10⁹/L)	M	1.65 ± 0.29	1.84 ± 0.90	1.86 ± 0.59	2.20 ± 0.42
		F	1.18 ± 0.57	1.01 ± 0.25	1.10 ± 0.64	1.41 ± 0.36
	BA (× 10⁹/L)	M	0.01 ± 0.01	0.00 ± 0.01	0.01 ± 0.01	0.01 ± 0.00
		F	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00
	EO (× 10⁹/L)	M	0.10 ± 0.03	0.08 ± 0.03	0.08 ± 0.04	0.10 ± 0.05
		F	0.10 ± 0.03	0.10 ± 0.03	0.08 ± 0.04	0.12 ± 0.05
	LY (× 10⁹/L)	M	12.31 ± 1.08	1.10 ± 2.36	12.66 ± 2.40	13.01 ± 1.10
		F	7.02 ± 1.13	9.56 ± 1.44	7.46 ± 1.82	8.30 ± 1.30
	MO (× 10⁹/L)	M	0.26 ± 0.07	0.23 ± 0.11	0.34 ± 0.11	0.33 ± 0.11
		F	0.12 ± 0.08	0.10 ± 0.06	0.14 ± 0.02	0.18 ± 0.05
Day 38	HGB (g/L)	M	145.70 ± 8.87	140.50 ± 26.82	149.60 ± 5.02	155.20 ± 8.38
		F	134.50 ± 5.35	151.50 ± 9.53	143.70 ± 3.49	142.70 ± 8.29
	RBC (× 10¹²/L)	M	7.39 ± 0.50	7.58 ± 0.73	7.68 ± 0.58	8.06 ± 0.34
		F	7.00 ± 1.27	7.66 ± 0.46	7.40 ± 0.24	7.50 ± 0.28
	WBC (× 10⁹/L)	M	10.69 ± 3.91	10.86 ± 1.50	9.01 ± 1.24	11.92 ± 4.08
		F	7.42 ± 2.87	10.32 ± 1.24*	8.65 ± 0.92	7.33 ± 2.14
	NE (× 10⁹/L)	M	0.71 ± 0.15	1.41 ± 0.54	1.05 ± 0.47	1.10 ± 0.33
		F	1.00 ± 0.50	1.00 ± 0.21	0.90 ± 0.33	1.00 ± 0.27
	BA (× 10⁹/L)	M	0.00 ± 0.01	0.00 ± 0.01	0.00 ± 0.00	0.00 ± 0.01
		F	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00	0.00 ± 0.00
	EO (× 10⁹/L)	M	0.05 ± 0.03	0.11 ± 0.09	0.04 ± 0.03	0.10 ± 0.05
		F	0.07 ± 0.03	0.11 ± 0.04	0.10 ± 0.15	0.09 ± 0.02
	LY (× 10⁹/L)	M	9.77 ± 3.84	9.03 ± 1.04	7.65 ± 0.85	10.23 ± 3.69
		F	6.09 ± 2.35	8.81 ± 0.83*	7.32 ± 0.90	6.02 ± 2.31
	MO (× 10⁹/L)	M	0.10 ± 0.05	0.18 ± 0.07	0.10 ± 0.04	0.11 ± 0.06
		F	0.10 ± 0.03*	0.16 ± 0.05	0.11 ± 0.04*	0.18 ± 0.07

Effects of rBoIFN-α on parenchymal organ indexes in Sprague Dawley rats in the sub-chronic toxicity test

Time	Organ	Gender	High-dose group	Middle-dose group	Low-dose group	Control group
Day 31	Heart	M	3.71 ± 0.28	3.61 ± 0.28	4.02 ± 0.42	3.60 ± 0.22

		F	3.71 ± 0.19	3.88 ± 0.57	3.66 ± 0.34	4.01 ± 0.43

	Liver	M	30.01 ± 3.19	31.53 ± 3.59	31.3 ± 2.28	28.14 ± 2.11

		F	33.78 ± 3.10	27.46 ± 4.40	28.19 ± 1.98	32.35 ± 5.27

	Spleen	M	1.80 ± 0.45	2.01 ± 0.40	2.01 ± 0.21	1.76 ± 0.24

		F	2.01 ± 0.19	2.09 ± 0.49	2.27 ± 0.99	1.89 ± 0.23

	Lung	M	4.72 ± 0.37	5.00 ± 0.54	4.61 ± 0.41	4.30 ± 1.08

		F	5.54 ± 0.79	5.01 ± 0.83	5.00 ± 0.24	5.82 ± 0.79

	Kidney	M	7.67 ± 1.24	7.53 ± 0.64	7.64 ± 0.30	7.53 ± 0.70

		F	7.52 ± 0.35	7.50 ± 1.54	6.35 ± 1.96	7.34 ± 0.83

	Stomach	M	8.74 ± 1.47	8.85 ± 1.64	9.30 ± 1.39	9.30 ± 1.39

		F	9.58 ± 3.20	8.44 ± 1.14	7.10 ± 1.32	7.83 ± 1.73

	Intestines	M	64.34 ± 11.54	64.52 ± 5.79	65.48 ± 16.00	63.52 ± 3.26

		F	55.22 ± 12.14	59.91 ± 11.92	58.32 ± 6.33	65.08 ± 9.62

	Testis	M	11.91 ± 0.70	12.02 ± 0.62	12.26 ± 1.44	12.62 ± 1.00

	Uterus and ovaries	F	3.72 ± 1.13	4.24 ± 0.73	3.88 ± 0.80	3.14 ± 0.63

Day 38	Heart	M	3.45 ± 0.98	3.42 ± 0.21	3.35 ± 0.34	3.55 ± 0.47

		F	3.59 ± 0.53	3.60 ± 0.29	3.80 ± 0.58	3.71 ± 0.45

	Liver	M	33.01 ± 1.98	31.85 ± 2.72	32.61 ± 2.83	32.06 ± 1.23

		F	27.84 ± 3.20	29.50 ± 2.41	31.15 ± 2.75	29.31 ± 2.26

	Spleen	M	1.76 ± 0.17	1.65 ± 0.17	2.01 ± 0.21	2.01 ± 0.43

		F	1.83 ± 0.37	2.01 ± 0.10	2.17 ± 0.91	1.80 ± 0.25

	Lung	M	4.16 ± 0.47	4.42 ± 0.57	4.25 ± 0.36	5.01 ± 1.10

		F	4.27 ± 0.29	4.65 ± 0.38	4.41 ± 0.24	4.64 ± 0.44

	Kidney	M	6.74 ± 0.30	7.04 ± 0.57	6.77 ± 0.17	7.25 ± 0.36

		F	6.59 ± 0.88	6.59 ± 0.58	7.03 ± 0.43	6.72 ± 0.64

	Stomach	M	8.66 ± 1.72	7.78 ± 0.82	8.58 ± 1.45	8.53 ± 0.71

		F	8.33 ± 0.86	8.07 ± 0.89	7.49 ± 1.18	7.68 ± 1.74

	Intestines	M	64.31 ± 8.66	66.15 ± 8.74	66.88 ± 8.01	66.81 ± 7.93

		F	61.07 ± 4.78	64.68 ± 11.63	58.82 ± 4.52	66.23 ± 6.21

	Testis	M	9.59 ± 0.35*	10.33 ± 0.70	9.75 ± 0.43	10.39 ± 0.56

	Uterus and ovaries	F	3.00 ± 0.74	2.85 ± 0.19	3.32 ± 0.49	3.04 ± 0.85

Acute and sub-chronic toxicity study of recombinant bovine interferon alpha in rodents

Figures & Tables

Fig. 1

Fig. 2

Fig. 3

Effects of rBoIFN-α on blood biochemical indexes in Sprague Dawley rats in the sub-chronic toxicity test

Effects of rBoIFN-α on haematological indexes in Sprague Dawley rats in the sub-chronic toxicity test

Effects of rBoIFN-α on parenchymal organ indexes in Sprague Dawley rats in the sub-chronic toxicity test

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