Long-term toxicological studies on the Chinese medicine 2036 Specialty-Qiangxin recipe in rats

Figures & data

Figure 1. Effects of oral 2036S-QXR on body weight during the 26-week period of administration and at the end of the 4-week recovery period. (A) Changes in body weight in female rats. (B) Changes in body weight in male rats. The number of female and male animals in each group (0–13 weeks) was 15. The number of female and male animals in each group (13–26 weeks) was 10. The number of female and male animals in each group at the end of the 4-week recovery period (30 weeks) was 3. There were no significant differences in the bodyweight of males and females in the treatment groups compared with the control group (p > 0.05). Mean ± SD.

Table 1. Food intake (g/100g body weight/week) after the administration of 2036S-QXR.

Sexes	Time (weeks)	Mouse number	Control	0.6 g/kg	1.2 g/kg	2.4 g/kg
Female
	0	15	126.1	129.8	117.9	127.1
	1	15	118.7	131.6	108.5	124.3
	2	15	111.6	119.3	101.7	107.1
	3	15	109.8	106.2	103.5	104.9
	4	15	98.3	97.7	96.8	93.6
	6	15	83.4	79.4	77.8	83.5
	8	15	76.1	73.4	66.3	79.7
	13	15	68.1	59.8	56.9	72.2
	16	10	63.8	59.7	53.7	62.8
	20	10	54.9	57.1	52.9	57.7
	24	10	53.3	54.2	51.7	56.1
	26	10	54.7	52.8	55.5	54.6
	Recovery period	3	42.8	45.5	44.9	45.3
Male
	0	15	157.0	151.4	168.5	159.5
	1	15	122.4	121.6	122.0	125.3
	2	15	107.6	106.3	104.8	111.0
	3	15	91.8	94.2	94.2	94.6
	4	15	85.1	84.9	83.6	89.3
	6	15	64.5	64.6	65.8	65.9
	8	15	60.3	59.6	58.3	62.6
	13	15	50.2	49.3	49.9	52.5
	16	10	44.6	41.9	42.0	41.7
	20	10	42.8	42.4	41.2	43.7
	24	10	40.6	40.0	40.8	42.0
	26	10	42.4	43.9	44.4	44.9
	Recovery period	3	34.5	33.7	32.6	34.7

Note. Data represents the total food intake of all the mice in each group per week relative to their body weights. The p-values in all treatment groups were not significant compared with the control group (0 g/kg).

Table 2. Urinary analysis after the administration of 2036S-QXR.

Times	Sexes	Doses	pH	Occult blood				Nitrite				Urobilinogen				Bilirubin				Protein				Glucose				Ketones
				−	±	+	++	−	±	+	++	−	±	+	++	−	±	+	++	−	±	+	++	−	±	+	++	−	±	+	++
13 weeks	Female	Control	6.00 ± 0.00	5				5				5				5				5				5				5
		2.4 g/kg	6.40 ± 0.55	5				5				5				5				5				5				5
	Male	Control	6.00 ± 0.00	5				5				5				5				5				5				5
		2.4 g/kg	6.00 ± 0.00	5				5				5				5				5				5				5
26 weeks	Female	Control	6.14 ± 0.38	7				7				7				7				5	1	1		7				7
		0.6 g/kg	6.71 ± 0.76	7				7				7				7				6	1			7				7
		1.2 g/kg	6.57 ± 0.53	7				7				7				7				6	1			7				7
		2.4 g/kg	6.28 ± 0.76	7				7				7				7				4		2	1	7				7
	Male	Control	6.28 ± 0.49	7				7				7				7				5	1	1		7				7
		0.6 g/kg	6.14 ± 0.38	7				7				7				7				6	1			7				7
		1.2 g/kg	6.42 ± 0.53	7				7				7				7				6	1			7				7
		2.4 g/kg	6.42 ± 0.53	7				7				7				7				4		2	1	7				7
Recovery period	Female	Control	6.00 ± 0.00	3				3				3				3				3				3				3
		0.6 g/kg	6.00 ± 0.00	3				3				3				3				3				3				3
		1.2 g/kg	5.67 ± 0.58	3				3				3				3				3				3				3
		2.4 g/kg	6.33 ± 0.58	3				3				3				3				3				3				3
	Male	Control	6.00 ± 0.00	3				3				3				3				3				3				3
		0.6 g/kg	6.00 ± 0.00	3				3				3				3				3				3				3
		1.2 g/kg	6.33 ± 0.58	3				3				3				3				3				3				3
		2.4 g/kg	6.33 ± 0.58	3				3				3				3				3				3				3

Note. pH value is mean ± SD. The p-values in all treatment groups were not significant compared with the control group using Fisher’s exact test.

Figure 2. Hematological parameters of the rats after administration of 2036S-QXR for 13 and 26 weeks, and at the end of the recovery period. *p < 0.05 and **p < 0.01 as compared to the control group (0 g/kg). Mean ± SD. n = 5 for 13 weeks, n = 7 for 26 weeks, and n = 3 for the recovery period.

Table 3. Incidence of histopathological lesions in various organs after the administration of 2036S-QXR for 26 weeks and at the end of the recovery period.

Organs	Microscopic findings	Control	0.6 g/kg	1.2 g/kg	2.4 g/ml
Heart	Normal	20/20	20/20	20/20	20/20
Liver	Cell infiltration (slight)	10/20	10/20	6/20	9/20
Lung	Interstitial pneumonia (slight); cell infiltration (slight)	11/20	11/20	11/20	7/20
Spleen	Normal	20/20	20/20	20/20	20/20
Kidney	Basophilic lesions; Scattered interstitial nephritis; dilated tubules; protein casts (slight)	9/20	7/20	6/20	10/20
Bladder	Normal	20/20	20/20	20/20	20/20
Adrenal	Normal	20/20	20/20	20/20	20/20
Stomach	Normal	20/20	20/20	20/20	20/20
Duodenum	Normal	20/20	20/20	20/20	20/20
Jejunum	Normal	20/20	20/20	20/20	20/20
Ileum	Normal	20/20	20/20	20/20	20/20
Uterus	Normal	10/10	10/10	10/10	10/10
Ovary	Normal	10/10	10/10	10/10	10/10
Testis	Accumulation of macrophages (slight)	0/10	0/10	2/10	0/10
Epididymis	Normal	10/10	10/10	10/10	10/10
Prostate	Chronic prostatitis (slight)	3/10	1/10	2/10	2/10
Cerebrum	Normal	20/20	20/20	20/20	20/20
Cerebellum	Normal	20/20	20/20	20/20	20/20
Pituitary	Normal	20/20	20/20	20/20	20/20
Thymus	Thymus atrophy; vesicles (slight)	2/20	2/20	4/20	5/20
Pancreas	Normal	20/20	20/20	20/20	20/20
Thyroid	Normal	20/20	20/20	20/20	20/20
Parathyroid	Normal	20/20	20/20	20/20	20/20

Note. Data are n/N, n represents the animal number that has the histopathological finding and N represents the total animal number examined.

Figure 3. Biochemical parameters of rats after administration of 2036S-QXR for 13 and 26 weeks, and at the end of the recovery period. *p < 0.05 and **p < 0.01 as compared to the control group (0 g/kg). Mean ± SD. n = 5 for 13 weeks, n = 7 for 26 weeks, and n = 3 for the recovery period.

Figure 4. Effects of oral 2036S-QXR on the relative organ weight (g/100 g body weight). The p-values in all treatment groups were not significant compared with the control group. Mean ± SD. n = 5 for 13 weeks, n = 7 for 26 weeks, and n = 3 for the recovery period.

Figure 5. Histopathological organ examination after administration of 2036S-QXR using haematoxylin and eosin staining (10×). (A) Representative images of liver sections. (B) Representative images of kidney sections. (C) Representative images of heart sections. (D) Representative images of brain sections. (E) Representative images of lung sections. (F) Representative images of thymus sections. (G) Representative images of intestinal sections. (H) Representative images of prostate sections.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.