Sub-chronic toxicity study of the methanol root extract of Cnestis ferruginea

Figures & data

Table 1.  Effects of C. ferruginea on sperm parameters and change in body weight of rats over 90 days.

Treatment	Dose (mg/kg)	Sperm motility	Sperm count (×10^6)	Abnormality (%)	Mean change in weight of rats over 90 days (g)
					Male	Female
Main study
DW	-	65.00 ± 7.50	22.00 ± 3.00	6.00 ± 1.20	40.00 ± 5.40	42.00 ± 6.00
CF	80	51.00 ± 4.30	14.00 ± 0.68	2.80 ± 1.10	39.00 ± 4.20	52.00 ± 5.50
	400	45.00 ± 17.00	20.00 ± 0.31	7.00 ± 1.80	42.00 ± 5.10	44.00 ± 5.00
	1000	31.00 ± 9.70	10.00 ± 3.10^b	8.20 ± 1.90	16.00 ± 2.80^a,c,d	47.77 ± 6.26^e
Reversibility study
DW	-	68.33 ± 10.14	24.90 ± 0.67	0.00 ± 0.00
CF	80	48.33 ± 4.410	11.33 ± 1.64^a	0.00 ± 0.00
	400	60.00 ± 10.00	19.75 ± 0.25	0.50 ± 0.50
	1000	IND	IND	IND

Values are mean ± SEM (n = 4–5, main study; 2–3, reversibility study).

^ap < 0.05, ^bp < 0.01 vs. control.

^cp < 0.05 vs. CF 80 mg/kg.

^dp < 0.01 vs. CF 400 mg/kg.

^ep < 0.001 vs. CF 1000 mg/kg male rats.

CF, C. ferruginea; DW, distilled water; IND, insufficient data for analysis.

Table 2.  Effects of C. ferruginea on weight of vital organs.

Treatment	Dose (mg/kg)	Male					Female
		Brain	Heart	Liver	Kidney	Testes	Brain	Heart	Liver	Kidney	Ovary
Main study
DW	(10 mL/kg)	0.70 ± 0.04	0.33 ± 0.01	4.10 ± 0.25	0.33 ± 0.03	0.76 ± 0.07	0.77 ± 0.04	0.30 ± 0.01	5.00 ± 0.18	0.24 ± 0.03	0.04 ± 0.00
CF	80	0.50 ± 0.01	0.34 ± 0.02	3.30 ± 0.37	0.29 ± 0.02	0.79 ± 0.14	1.10 ± 0.06^b,h	0.33 ± 0.01	3.70 ± 0.09^b	0.33 ± 0.01	0.06 ± 0.01
	400	0.71 ± 0.02	0.32 ± 0.02	3.20 ± 0.20	0.41 ± 0.11	0.69 ± 0.05	0.75 ± 0.08^e	0.44 ± 0.08	3.10 ± 0.28^c	0.36 ± 0.06	0.10 ± 0.00^c,e
	1000	0.70 ± 0.03	0.29 ± 0.01	3.80 ± 0.27	0.35 ± 0.10	0.38 ± 0.05^a,d,g	0.71 ± 0.05^f	0.36 ± 0.02	3.70 ± 0.16^b	0.31 ± 0.02	0.07 ± 0.01^g
Reversibility study
DW	(10 mL/kg)	1.03 ± 0.13	0.34 ± 0.02	3.92 ± 0.48	0.37 ± 0.03	0.64 ± 0.01	1.07 ± 0.09	0.30 ± 0.02	3.27 ± 0.34	0.31 ± 0.02	0.05 ± 0.01
CF	80	0.93 ± 0.07	0.34 ± 0.05	3.93 ± 0.74	0.37 ± 0.04	0.48 ± 0.02	1.06 ± 0.06	0.36 ± 0.03	3.82 ± 0.17	0.52 ± 0.23	0.07 ± 0.02
	400	0.83 ± 0.09	0.36 ± 0.02	3.81 ± 0.01	0.37 ± 0.04	0.80 ± 0.19	1.16 ± 0.07	0.35 ± 0.00	3.50 ± 0.02	0.34 ± 0.04	0.10 ± 0.03
	1000	IND	IND	IND	IND	IND	1.00 ± 0.07	0.28 ± 0.02	2.92 ± 0.04	0.32 ± 0.07	0.06 ± 0.01

Values are mean ± SEM (n = 4–5, main study; 2–3, reversibility study, per sex).

^ap < 0.05, ^bp < 0.01, ^cp < 0.001 vs. control.

^dp < 0.05, ^ep <.01, ^fp < 0.001 vs. CF 80 mg/kg.

^gp < 0.05 vs. CF 400 mg/kg.

^hp < 0.001 vs. CF 80 mg/kg (male).

Abbreviations: CF, C. ferruginea; DW, distilled water; IND, insufficient data for analysis.

Table 3.  Effects of C. ferruginea on organ in vivo antioxidant enzymes and MDA and GSH levels.

Treatment	Dose (mg/kg)	Organ	Male				Female
			GSH (U/mg protein)	SOD (U/mg protein)	CAT (U/mg protein)	MDA (U/mg protein)	GSH (U/mg protein)	SOD (U/mg protein)	CAT (U/mg protein)	MDA (U/mg protein)
DW	(10 mL/kg)	Liver	62.32 ± 6.23	108.80 ± 15.39	437.50 ± 61.87	26.38 ± 4.38	58.86 ± 15.52	206.80 ± 37.17	831.30 ± 149.40	39.93 ± 7.96
CF	80		91.74 ± 1.20	87.55 ± 0.29	351.70 ± 1.67	51.05 ± 0.25	120.60 ± 4.29	72.43 ± 14.33^a	406.00 ± 90.66	33.24 ± 6.09
	400		59.60 ± 5.78	84.16 ± 55.99	326.70 ± 230.50	41.58 ± 8.52	96.17 ± 11.05	67.05 ± 14.65^a	276.40 ± 56.67^a	27.62 ± 5.22
	1000		337.40 ± 89.91^c,f,i	132.00 ± 60.60	484.20 ± 207.40	24.48 ± 6.10	259.70 ± 30.98^b,d,h	112.80 ± 13.19	441.70 ± 50.69	25.90 ± 1.40
DW	(10 mL/kg)	Kidney	57.24 ± 15.84	55.86 ± 6.45	320.80 ± 77.17	27.86 ± 2.75	31.44 ± 12.40	65.30 ± 21.77	262.50 ± 87.50	34.43 ± 6.89
CF	80		157.60 ± 57.46	43.53 ± 21.77	175.00 ± 87.50	31.12 ± 3.17	60.30 ± 4.07	90.33 ± 25.65	516.30 ± 230.60	34.36 ± 4.55
	400		244.00 ± 95.53	171.20 ± 23.35	729.20 ± 77.17	32.00 ± 7.49	130.50 ± 15.17	129.90 ± 41.15	455.00 ± 76.45	19.53 ± 4.57
	1000		43.12 ± 4.50^g	33.81 ± 15.89^g	145.80 ± 60.81	39.06 ± 9.09	99.00 ± 19.37	54.41 ± 10.88	288.80 ± 61.25	31.05 ± 5.94
DW	(10 mL/kg)	Brain	250.00 ± 73.76	65.30 ± 21.77	262.50 ± 87.50	28.98 ± 8.74	253.50 ± 45.40	70.74 ± 34.84	284.40 ± 140.10	31.02 ± 13.13
CF	80		177.70 ± 27.61	46.00 ± 10.50	184.90 ± 42.22	30.06 ± 4.68	248.10 ± 108.50	67.47 ± 31.62	271.30 ± 127.10	33.85 ± 10.08
	400		125.90 ± 59.50	111.00 ± 61.73	446.30 ± 248.20	30.85 ± 10.44	350.50 ± 27.43	54.41 ± 6.28	218.80 ± 25.62	36.15 ± 2.69
	1000		352.70 ± 36.13	49.30 ± 13.29	198.20 ± 53.43	43.71 ± 11.14	82.34 ± 42.45	32.65 ± 10.88	131.30 ± 43.75	20.76 ± 10.53
DW	(10 mL/kg)	Testes/ovary	262.60 ± 23.02	54.41 ± 6.28	218.80 ± 25.26	9.82 ± 1.40	110.50 ± 54.20	58.04 ± 26.16	243.30 ± 98.55	25.02 ± 12.82
CF	80		299.00 ± 14.22	195.90 ± 0.00	787.50 ± 0.00	25.25 ± 1.69^a	95.59 ± 11.70	217.70 ± 36.64^a	953.80 ± 150.60^a	19.51 ± 7.42
	400		187.30 ± 41.07	133.90 ± 62.79	538.10 ± 252.40	14.75 ± 5.68	374.20 ± 10.01^b,e	191.70 ± 4.50	980.00 ± 17.50^a	15.01 ± 3.54
	1000		71.50 ± 17.81^b,f,g	160.00 ± 43.83^g	643.10 ± 176.20	15.36 ± 1.86	326.10 ± 10.59^a,e	43.53 ± 0.00^α	218.80 ± 43.75^d,g	13.97 ± 0.74

Values are mean ± SEM (n = 4–5 per sex).

^ap < 0.05, ^bp < 0.01, ^cp < 0.001 vs. control.

^dp < 0.05, ^ep < 0.01, ^fp < 0.001 vs. CF 80 mg/kg.

^gp < 0.05, ^hp < 0.01, ⁱp < 0.001 vs. CF 400 mg/kg.

Generally, there were no significant differences (p > 0.05) between corresponding values in male and female rats. DW, distilled water; CF, C. ferruginea; MDA, malondialdehyde; SOD, superoxide dismutase.

Table

Treatment	Dose (mg/kg)	Organ	Observation	Interpretation
DW	-	Heart	Normal	1. The heart muscle (myocytes) seen are normal, composed of interlacing fascicles or syncitium of myocardial cells which are elongated, with spindle nuclei.
		Kidney	Normal	2. Histologic section of kidney showed cellular tufts of glomeruli surrounded by Bowman’s spaces, disposed on a background that contained tubules cut in varying planes (Figure 1).
		Liver	Normal	3. Histologic section of liver showed preserved normal hepatic architecture with hepatocytes arranged in plates. There was no vascular congestion, no areas of necrosis or hemorrhage. No fatty change or fibrosis was seen. The portal tracts contained the hepatic triads (artery, vein, and bile duct), and scant inflammatory cellular infiltrates (Figure 2).
		Testes	Normal	4. The seminiferous tubules were normal sized, lined by 4–5 cell layer thick spermatogenic series cells, and contained numerous spermatids within their lumina. The interstitial cells of Leydig were also normal (Figure 3).
		Ovary	Normal	5. The histology of the ovary consisted of spindle-shaped cells, fine collagen fibers and ground substance that together constituted the ovarian stroma. The stromal cells resembled fibroblasts but some contained lipid droplets. Bundles of smooth muscle cells were also scattered throughout the stroma. In the peripheral zone of the stroma, known as the cortex, were numerous follicles that contained female gametes in various stages of development. In addition, there were postovulatory follicles of various kinds, namely corpora lutea.
CF	80	Heart	Normal	As in 1 above.
		Kidney	Congested (M) Normal (F)	Dilatation and engorgement/distension of blood vessels within the interstitium by blood (Figure 4). As in 2 above.
		Liver	Congested (M) Normal (F)	Histologic section of liver showed prominent hepatic sinusoids which were engorged with red blood cells (Figure 5).As in 3 above.
		Testes	Normal	As in 4 above.
		Ovary	Normal	As in 5 above.
CF	400	Heart	Normal	As in 1 above.
		Kidney	Congested (M)	Dilatation and engorgement/distension of blood vessels within the interstitium by blood (Figure 6).
			Normal (F)	As in 2 above.
		Liver	Intracellular accumulations/Fatty change (M)	The hepatocytes stained less with eosin, their cytoplasm appeared glassy and contained inclusions, possibly lipid (Figure 7).
			Normal (F)	As in 3 above.
		Testes	Normal	As in 4 above.
		Ovary	Normal	As in 5 above.
CF	1000	Heart	Normal	As in 1 above.
		Kidney	Normal	As in 2 above.
		Liver	Intracellular accumulations/Fatty change (M)Normal (F)	The hepatocytes stained less with eosin, their cytoplasm appeared glassy and contained inclusions, possibly lipid (Figure 8). As in 3 above.
		Testes	Inflammation/necrosis	Dead cells and amorphous debris seen with aggregation of inflammatory cells (Figure 9).
		Ovary	Normal	As in 5 above.

M, male; F, female; DW, distilled water.

Figure 1.  Histopathologic presentation of male rat kidney of control group (Normal; 400×).

Figure 2.  Histopathologic presentation of male rat liver of control group (Normal; 400×).

Figure 3.  Histopathologic presentation of rat testes of control group (Normal; 400×).

Figure 4.  Histopathologic presentation of male rat kidney of CF 80 mg/kg group (Congested; 400×).

Figure 5.  Histopathologic presentation of male rat liver of CF 80 mg/kg group (Congested; 400×).

Figure 6.  Histopathologic presentation of male rat kidney of CF 400 mg/kg group (Congested; 400×).

Figure 7.  Histopathologic presentation of male rat liver of CF 400 mg/kg group (Intracellular accumulations/Fatty change; 400×).

Figure 8.  Histopathologic presentation of male rat liver of CF 1000 mg/kg group (Intracellular accumulations/Fatty change; 400×).

Figure 9.  Histopathologic presentation of rat testes of CF 1000 mg/kg group (Inflammation/necrosis; 400×).

Figure 10.  Histopathologic presentation of male rat kidney of CF 80 mg/kg group, reversibility study (Normal; 400×).

Figure 11.  Histopathologic presentation of male rat liver of CF 1000 mg/kg group, reversibility study (Congested; 400×).

Figure 12.  Histopathologic presentation of rat testes of CF 80 mg/kg group, reversibility study (Calcifications; 400×).

Table 4.  Effects of C. ferruginea on hematological parameters (main study).

Treatment	Dose (mg/kg)	Sex	RBC (10^6/µL)	Hb (g/dL)	PCV (%)	MCV (fL)	MCH (pg)	MCHC (%)	MPV (fL)	Platelet (10^5/µL)
DW	-	Male	6.51 ± 0.40	11.74 ± 0.60	38.68 ± 1.94	59.72 ± 1.45	17.98 ± 0.43	30.10 ± 0.04	7.80 ± 0.30	510.80 ± 73.02
CF	80		6.95 ± 0.54	12.00 ± 0.40	40.25 ± 2.15	58.05 ± 1.35	17.35 ± 0.75	29.80 ± 0.60	7.75 ± 0.05	471.50 ± 329.50
	400		7.35 ± 0.28	13.75 ± 1.24	41.65 ± 1.94	56.63 ± 0.67	17.03 ± 0.08	30.05 ± 0.27	7.53 ± 0.15	527.00 ± 78.00
	1000		7.14 ± 0.54	12.15 ± 0.76	39.58 ± 1.59	57.33 ± 1.01	17.08 ± 0.21	29.75 ± 0.37	7.53 ± 0.21	239.80 ± 102.40
DW	-	Female	5.87 ± 0.27	10.72 ± 0.83	35.62 ± 1.82	60.64 ± 1.15	18.20 ± 0.91	29.90 ± 1.05	7.80 ± 0.14	419.40 ± 29.32
CF	80		6.42 ± 0.20	11.54 ± 0.25	38.12 ± 1.33	59.34 ± 0.86	18.02 ± 0.52	30.36 ± 0.75	7.80 ± 0.17	404.40 ± 96.82
	400		6.44 ± 0.32	11.15 ± 0.45	36.48 ± 1.56	56.73 ± 1.20	17.33 ± 0.33	23.83 ± 6.81	7.28 ± 0.33	460.40 ± 173.80
	1000		6.67 ± 0.65	11.85 ± 0.99	39.50 ± 3.73	59.33 ± 1.35	17.85 ± 0.44	30.10 ± 0.36	7.75 ± 0.17	510.00 ± 181.90
	Dose (mg/kg)		RDW (%)	PDW (%)	WBC (10^3/µL)	WBC differential (%)
						L	M	N	E	B
DW	-	Male	37.46 ± 1.32	9.44 ± 0.49	11.96 ± 3.20	66.48 ± 6.19	5.96 ± 1.05	24.34 ± 5.41	3.22 ± 0.56	0
CF	80		36.75 ± 1.35	9.80 ± 0.40	9.55 ± 1.25	62.75 ± 2.15	3.85 ± 0.35	32.05 ± 1.55	1.35 ± 0.25	0
	400		32.73 ± 1.15^a	9.05 ± 0.20	8.83 ± 2.76	53.25 ± 5.17	8.10 ± 1.31	35.53 ± 5.22	3.88 ± 0.52	0
	1000		32.85 ± 0.88^a	9.08 ± 0.28	9.73 ± 1.15	58.23 ± 4.61	6.25 ± 0.82	32.53 ± 4.25	3.00 ± 0.44	0
DW	-	Female	32.18 ± 0.66	9.90 ± 0.35	9.32 ± 0.73	68.22 ± 1.01	4.92 ± 0.77	24.78 ± 0.98	2.28 ± 0.36	0
CF	80		31.86 ± 0.56	8.34 ± 1.70	6.52 ± 0.44	69.08 ± 0.87	3.88 ± 0.56	26.92 ± 3.18	2.12 ± 0.45	0
	400		31.53 ± 0.90	8.73 ± 0.56	4.90 ± 1.13	64.58 ± 9.60	3.70 ± 0.78^b	29.88 ± 9.62	3.10 ± 0.80	0
	1000		32.45 ± 1.24	9.78 ± 0.29	11.30 ± 2.62	75.35 ± 3.37	3.40 ± 0.96	20.13 ± 1.98	1.13 ± 0.48	0

Values are mean ± SEM (n = 4–5 per sex).

^ap < 0.05 vs. control value.

^bp < 0.05 vs. corresponding value for male rats.

Abbreviations: CF, C. ferruginea; DW, distilled water; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; MPV, mean platelet volume; PCV, packed cell volume; PDW, platelet distribution width; RDW, red cell distribution width.

Table 5.  Effects of C. ferruginea on hematological parameters (reversibility study).

Treatment	Dose (mg/kg)	Sex	RBC (10^6/µL)	Hb (g/dL)	PCV (%)	MCV (fL)	MCH (pg)	MCHC (%)	MPV (fL)	Platelet (10^5/µL)
DW	-	Male	7.38 ± 0.25	13.43 ± 0.03	45.07 ± 0.03	60.17 ± 1.70	17.70 ± 0.60	29.80 ± 0.06	8.27 ± 0.07	831.30 ± 23.10
CF	80		7.96 ± 0.02	13.80 ± 0.31	46.20 ± 0.53	58.17 ± 0.55	17.20 ± 0.32	29.63 ± 0.29	8.03 ± 0.03	820.70 ± 40.42
	400		7.82 ± 0.51	14.20 ± 0.60	46.45 ± 1.65	59.50 ± 1.80	18.20 ± 0.40	30.60 ± 0.20	7.60 ± 0.10^a	798.50 ± 90.50
	1000		ID	ID	ID	ID	ID	ID	ID	ID
DW	-	Female	7.84 ± 0.28	14.67 ± 0.37	48.20 ± 1.37	61.53 ± 1.48	18.70 ± 0.23	30.47 ± 0.41	7.80 ± 0.21	898.30 ± 124.30
CF	80		7.09 ± 0.10	12.43 ± 0.30^b	41.23 ± 0.49^c,b	58.27 ± 0.17	17.60 ± 0.15	30.43 ± 0.37	7.53 ± 0.07	836.00 ± 4.62
	400		7.41 ± 0.06	13.05 ± 0.05	44.10 ± 0.70	59.00 ± 1.00	17.60 ± 0.10	29.60 ± 0.40	8.50 ± 0.20^c,a,e	818.00 ± 32.00
	1000		8.24 ± 0.21	14.35 ± 0.15^d	47.80 ± 0.00^e	58.05 ± 1.45	17.45 ± 0.25	30.00 ± 0.30	8.35 ± 0.05^d	1062.00 ± 102.00
	Dose (mg/kg)		RDW (%)	PDW (%)	WBC (10^3/μL)	WBC differential (%)
						L	M	N	E	B
DW	-	Male	39.70 ± 0.50	10.23 ± 0.09	10.47 ± 1.56	63.27 ± 5.41	5.00 ± 0.55	28.63 ± 5.75	3.13 ± 0.09	0
CF	80		38.23 ± 0.13	9.97 ± 0.12	18.01 ± 0.81	74.20 ± 0.32	5.37 ± 0.20	15.33 ± 0.20	5.00 ± 0.00	0
	400		37.35 ± 0.65	9.15 ± 0.05	15.50 ± 3.30	72.40 ± 1.00	6.20 ± 2.50	46.75 ± 24.25	4.65 ± 2.25	0
	1000		IND	IND	IND	IND	IND	IND	IND	0
DW	-	Female	36.73 ± 4.25	9.57 ± 0.50	6.47 ± 0.34	68.23 ± 3.24	4.90 ± 0.96	26.33 ± 4.94	2.87 ± 0.22	0
CF	80		33.50 ± 0.84	9.20 ± 0.06	9.17 ± 1.16	70.70 ± 0.91	5.00 ± 0.72	21.87 ± 0.20	2.37 ± 0.09	0
	400		34.25 ± 0.55	10.70 ± 0.40	9.25 ± 3.85	69.50 ± 12.20	6.65 ± 0.65	20.25 ± 11.05	3.60 ± 0.50	0
	1000		34.70 ± 0.10	10.90 ± 0.60^d	7.80 ± 4.40	64.00 ± 7.40	5.50 ± 2.00	5.76 ± 3.45	2.50 ± 0.50	0

Values are mean ± SEM (n = 2–3 per sex).

^ap < 0.05, ^bp < 0.01 vs. control value.

^cp < 0.05 vs. corresponding value for male rats.

^dp < 0.05, ^ep < 0.01 vs. CF 80 mg/kg.

Abbreviations: CF, C. ferruginea; DW, distilled water; IND, insufficient data for analysis; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; MPV, mean platelet volume; PDW, platelet distribution width; PCV, packed cell volume; RDW, red cell distribution width.

Table 6.  Effects of C. ferruginea on serum biochemical parameters (main study).

Treatment	Dose (mg/kg)	Male				Female
		AST (U/L)	ALT (U/L)	ALP (U/L)	Total bilirubin (mmol/L)	AST (U/L)	ALT (U/L)	ALP (U/L)	Total bilirubin (mmol/L)
DW	-	238.50 ± 28.86	102.00 ± 26.00	254.60 ± 36.36	5.98 ± 0.15	216.30 ± 15.74	108.20 ± 8.87	201.90 ± 38.51	4.94 ± 0.17
CF	80	130.00 ± 24.30	56.90 ± 6.90	216.90 ± 13.53	6.30 ± 0.59	240.90 ± 31.43	91.64 ± 5.36	237.10 ± 27.42	5.50 ± 0.35
	400	175.50 ± 13.92	77.20 ± 15.89	279.90 ± 37.88	6.39 ± 0.33	278.10 ± 50.03	192.10 ± 78.41	272.30 ± 51.84	5.78 ± 0.32
	1000	201.60 ± 12.20	88.38 ± 9.24	253.10 ± 39.83	6.47 ± 0.10	266.50 ± 20.39	110.80 ± 12.70	261.00 ± 19.58	6.45 ± 0.35^a
		Total protein (g/L)	Albumin (g/)	Total cholesterol (mmol/L)	Triglyceride (mmol/L)	Total protein (g/L)	Albumin (g/L)	Total cholesterol (mmol/L)	Triglyceride (mmol/L)
DW	-	63.74 ± 9.44	32.32 ± 1.48	1.52 ± 0.08	0.72 ± 0.07	91.50 ± 2.29	44.50 ± 1.64	1.75 ± 0.10	0.97 ± 0.22
CF	80	80.75 ± 2.05	34.60 ± 1.70	1.55 ± 0.05	0.54 ± 0.03	89.68 ± 2.50	37.32 ± 1.52	2.01 ± 0.09	0.73 ± 0.06
	400	77.25 ± 2.66	32.05 ± 1.85	1.49 ± 0.06	0.78 ± 0.16	97.58 ± 7.18	34.93 ± 4.32	1.86 ± 0.32	0.76 ± 0.15
	1000	68.14 ± 2.83	28.98 ± 1.10	1.21 ± 0.12	0.75 ± 0.05	85.30 ± 3.92	37.03 ± 2.75	1.86 ± 0.19	1.03 ± 0.06
		Creatinine (µmol/L)	Urea (mmol/L)	Uric acid		Creatinine (µmol/L)	Urea (mmol/L)	Uric acid
DW	-	60.48 ± 1.89	5.94 ± 0.76	116.10 ± 17.83		78.36 ± 1.96	6.20 ± 0.51	65.88 ± 11.47
CF	80	77.74 ± 3.06	7.30 ± 0.90	100.60 ± 7.59		80.87 ± 4.13	6.42 ± 0.64	83.82 ± 6.22
	400	74.38 ± 1.65	5.25 ± 0.39	137.20 ± 19.31		74.94 ± 4.83	6.73 ± 0.93	162.10 ± 28.45
	1000	66.54 ± 3.75	6.80 ± 0.54	185.20 ± 62.50		73.47 ± 6.04	5.78 ± 0.49	152.90 ± 8.35

Values are mean ± SEM (n = 4–5 per sex).

^ap < 0.05 vs. control.

Generally, there were no significant differences (p > 0.05) between corresponding values in male and female rats.

Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransaminase; AST, aspartate aminotransaminase; CF, C. ferruginea; DW, distilled water.

Table 7.  Effects of C. ferruginea on serum biochemical parameters (reversibility study).

Treatment	Dose (mg/kg)	Male				Female
		AST (U/L)	ALT (U/L)	ALP (U/L)	Total bilirubin (mmol/L)	AST (U/L)	ALT (U/L)	ALP (U/L)	Total bilirubin (mmol/L)
DW	-	262.30 ± 14.15	152.40 ± 68.45	244.30 ± 52.38	2.84 ± 1.15	209.10 ± 17.05	106.00 ± 6.55	183.00 ± 1.53	2.58 ± 0.96
CF	80	179.50 ± 7.45	124.40 ± 13.45	356.40 ± 135.80	1.90 ± 0.46	255.40 ± 77.00	125.30 ± 31.20	185.70 ± 6.27	2.39 ± 0.54
	400	221.80 ± 44.80	169.80 ± 58.85	309.90 ± 10.74	2.70 ± 0.39	382.30 ± 105.10	319.90 ± 109.30	279.80 ± 16.70	1.81 ± 0.29
	1000	ID	ID	ID	ID	241.90 ± 26.35	149.00 ± 17.85	343.20 ± 36.30	3.54 ± 0.14
		Total protein (g/L)	Albumin (g/)	Total cholesterol (mmol/L)	Triglyceride (mmol/L)	Total protein (g/L)	Albumin (g/L)	Total cholesterol (mmol/L)	Triglyceride (mmol/L)
DW	-	75.00 ± 0.30	36.10 ± 3.00	1.83 ± 0.02	0.90 ± 0.04	88.80 ± 5.20	43.85 ± 0.25	2.54 ± 0.21	0.67 ± 0.22
CF	80	79.25 ± 5.55	35.75 ± 3.55	1.65 ± 0.22	1.19 ± 0.49	75.55 ± 8.35	36.60 ± 4.50	1.99 ± 0.30	0.87 ± 0.16
	400	81.00 ± 3.80	35.95 ± 1.65	1.92 ± 0.03	0.71 ± 0.25	83.50 ± 1.30	31.47 ± 1.44	2.09 ± 0.25	0.79 ± 0.08
	1000	ID	ID	ID	ID	82.55 ± 0.35	29.60 ± 4.40	1.48 ± 0.38	0.71 ± 0.17
		Creatinine (µmol/L)	Urea (mmol/L)	Uric acid		Creatinine (µmol/L)	Urea (mmol/L)	Uric acid
DW	-	64.26 ± 0.16	6.75 ± 1.55	74.24 ± 0.38		68.72 ± 3.79	9.15 ± 0.95	73.26 ± 1.06
CF	80	60.55 ± 4.85	6.65 ± 1.05	133.60 ± 37.18		66.35 ± 10.00	6.85 ± 2.45	141.90 ± 38.14
	400	62.74 ± 0.30	5.00 ± 0.40	49.19 ± 4.61		62.27 ± 2.51	5.97 ± 0.64	73.94 ± 7.93
	1000	ID	ID	ID		65.07 ± 0.06	5.60 ± 1.50	91.29 ± 33.87

Values are mean ± SEM (n = 2–3 per sex). Data were not significant (p > 0.05).

Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransaminase; AST, aspartate aminotransaminase; CF, C. ferruginea; DW, distilled water.