Bidens pilosa L. (Asteraceae) cultivated in Brazil on acute liver disease in dogs

Bidens pilosa L. is a medicinal plant popularly used for treatment of liver diseases. In this study, the dry extract of aerial parts of Bidens pilosa and Silymarin, a phytocomplex obtained from the Silybum marianum fruits and marketed as hepatoprotective, were tested in dogs experimentally acutely intoxicated with carbon tetrachloride. The liver activity was evaluated by hematological and biochemical profiles, and histological and ultrasound analyzes. It was observed that the lowest serum activities of ALT and serum concentrations of total bilirubin occurred in the groups treated with the dry extract of Bidens pilosa, while only decreased serum concentrations of total bilirubin occurred in the group treated with Silymarin. Best liver recovery was also observed for the dry extract of B. pilosa at a 400mg/Kg dose by ultrasonography. This study showed that the dry extract of Bidens pilosa acted more efficiently in the treatment of acute toxic hepatitis induced in dogs than Silymarin.

Keywords:
carbon tetrachloride; liver diseases; Bidens Pilosa

Authorship

A.V.C. Amaral

Medicina Veterinária, Universidade Federal de Jataí ˗ Jataí, GOUniversidade Federal de JataíBrazilJataí, GO, BrazilMedicina Veterinária, Universidade Federal de Jataí ˗ Jataí, GO

http://orcid.org/0000-0001-6406-2372

L.M.L. Parente

Medicina Veterinária, Universidade Salgado de Oliveira ˗ Goiânia, GOUniversidade Salgado de OliveiraBrazilGoiânia, GO, BrazilMedicina Veterinária, Universidade Salgado de Oliveira ˗ Goiânia, GO

http://orcid.org/0000-0001-6259-6311

E.C. Conceição

Faculdade de Farmácia, Universidade Federal de Goiás ˗ Goiânia, GOUniversidade Federal de GoiásBrazilGoiânia, GO, BrazilFaculdade de Farmácia, Universidade Federal de Goiás ˗ Goiânia, GO

http://orcid.org/0000-0003-4113-2686

J.R. Paula

Faculdade de Farmácia, Universidade Federal de Goiás ˗ Goiânia, GOUniversidade Federal de GoiásBrazilGoiânia, GO, BrazilFaculdade de Farmácia, Universidade Federal de Goiás ˗ Goiânia, GO

http://orcid.org/0000-0002-4424-7692

L.C. Cunha

Faculdade de Farmácia, Universidade Federal de Goiás ˗ Goiânia, GOUniversidade Federal de GoiásBrazilGoiânia, GO, BrazilFaculdade de Farmácia, Universidade Federal de Goiás ˗ Goiânia, GO

http://orcid.org/0000-0002-1525-8528

A.P.A. Costa

Aluna de Pós-Graduação em Ciência Animal, Universidade Federal de Goiás ˗ Goiânia, GOUniversidade Federal de GoiásBrazilGoiânia, GO, BrazilAluna de Pós-Graduação em Ciência Animal, Universidade Federal de Goiás ˗ Goiânia, GO

http://orcid.org/0000-0003-0386-806X

L.S. Oliveira

http://orcid.org/0000-0002-3344-2601

L.A.T. Benatti

Universidade do Oeste Paulista ˗ Presidente Prudente, SPUniversidade do Oeste PaulistaBrazilPresidente Prudente, SP, BrazilUniversidade do Oeste Paulista ˗ Presidente Prudente, SP

http://orcid.org/0000-0001-8238-8325

M.C.S. Fioravanti

Medicina Veterinária, Universidade Federal de Goiás ˗ Goiânia, GOUniversidade Federal de GoiásBrazilGoiânia, GO, BrazilMedicina Veterinária, Universidade Federal de Goiás ˗ Goiânia, GO

http://orcid.org/0000-0002-4993-5523

E-mail: andreiavcvet@hotmail.com

SCIMAGO INSTITUTIONS RANKINGS

Medicina Veterinária, Universidade Federal de Jataí ˗ Jataí, GOUniversidade Federal de JataíBrazilJataí, GO, BrazilMedicina Veterinária, Universidade Federal de Jataí ˗ Jataí, GO

Faculdade de Farmácia, Universidade Federal de Goiás ˗ Goiânia, GOUniversidade Federal de GoiásBrazilGoiânia, GO, BrazilFaculdade de Farmácia, Universidade Federal de Goiás ˗ Goiânia, GO

Universidade do Oeste Paulista ˗ Presidente Prudente, SPUniversidade do Oeste PaulistaBrazilPresidente Prudente, SP, BrazilUniversidade do Oeste Paulista ˗ Presidente Prudente, SP

Medicina Veterinária, Universidade Federal de Goiás ˗ Goiânia, GOUniversidade Federal de GoiásBrazilGoiânia, GO, BrazilMedicina Veterinária, Universidade Federal de Goiás ˗ Goiânia, GO

Figures | Tables

Figures (1)
Tables (2)

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Figure 1
Photomicrograph of a hydropic degeneration area of hepatocytes and necrosis in a liver of control group dog (A); microvacuolar degeneration and hepatocyte and blood vessel necrosis in the liver of a dog of the group treated with ethanolic extract of Bidens pilosa L. (Asteraceae) at a dose of 100 mg/kg (B); focal degeneration of the bile duct and inflammatory infiltrate near a bile duct in a dog of the group treated with silymarin (C); cholangitis in a dog treated with ethanolic extract of Bidens pilosa L. (Asteraceae) at a dose of 400 mg/kg (D), 48 hours after intoxication by CCl₄ in a single oral dose of 2.5mL/Kg. HE, 20X. Goiânia, Goiás, Brazil.

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Table 1
Mean values of ALT, AST, ALP and GGT of dogs (n=6) treated for 21 days with starch (400mg), dry extract of Bidens pilosa L. (Asteraceae) (EEB) (100 and 400mg/Kg) and Silymarin (30mg/Kg) after oral administration of CCL₄ (2.5mL/Kg), Goiânia, Goiás, Brazil

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Table 2
Mean values of direct bilirubin (directBB), total bilirubin (totalBB), total proteins (TP), globulin albumins and total cholesterol of dogs (n=6) treated for 21 days with starch (negative control), dry extract of Bidens pilosa L. (Asteraceae) (EEB) (100 and 400mg/Kg) and Silymarin (30mg/Kg) after oral administration of CCL₄ (2.5mL/Kg), Goiânia, Goiás, Brazil

Figure 1 Photomicrograph of a hydropic degeneration area of hepatocytes and necrosis in a liver of control group dog (A); microvacuolar degeneration and hepatocyte and blood vessel necrosis in the liver of a dog of the group treated with ethanolic extract of Bidens pilosa L. (Asteraceae) at a dose of 100 mg/kg (B); focal degeneration of the bile duct and inflammatory infiltrate near a bile duct in a dog of the group treated with silymarin (C); cholangitis in a dog treated with ethanolic extract of Bidens pilosa L. (Asteraceae) at a dose of 400 mg/kg (D), 48 hours after intoxication by CCl₄ in a single oral dose of 2.5mL/Kg. HE, 20X. Goiânia, Goiás, Brazil.

Table 1 Mean values of ALT, AST, ALP and GGT of dogs (n=6) treated for 21 days with starch (400mg), dry extract of Bidens pilosa L. (Asteraceae) (EEB) (100 and 400mg/Kg) and Silymarin (30mg/Kg) after oral administration of CCL₄ (2.5mL/Kg), Goiânia, Goiás, Brazil

	ALT	BL*	24h	48h	72h	5d	8d	11d	14d	17d	21d
Control	Mean	38.33^a	266.83^b	419.50^a	334.67^a	236.67^a	161.40^a	130.10^a	64.86^a	64.20^a	61.60^a
	Std. Dev.	6.77	75.68	133.05	83.11	109.73	53.05	102.50	27.70	18.71	12.24
	CV	17.67	28.36	31.72	24.83	46.36	32.87	78.78	42.70	29.15	19.87
EEB 400mg/Kg	Mean	44.08^a	267.33^b	253.67^a	138.33^b	150.83 ^a	118.33^a	74.17^a	65.28^a	60.50^a	58.33^a
	Std. Dev.	16.79	96.64	119.46	32.98	51.09	30.49	12.86	27.80	13.34	25.86
	CV	38.08	36.15	47.09	23.84	33.87	25.76	17.33	42.58	22.05	44.33
EEB 100mg/Kg	Mean	42.92^a	276.58^b	306.83^a	167.33^b	142.33 ^a	144.67^a	144.92^a	99.33^a	86.33^a	79.67^a
	Std. Dev.	10.95	83.32	75.34	79.38	49.01	48.23	68.42	61.58	36.14	40.06
	CV	25.52	30.13	24.55	47.44	34.44	33.34	47.21	61.99	41.86	50.28
Silymarin	Mean	39.00^a	434.17^b	422.33^b	224.33^a	182.83^a	159.17^a	98.67^a	71.50^a	67.50^a	61.50^a
	Std. Dev.	10.88	142.67	70.66	89.76	41.83	52.93	40.44	34.41	20.95	18.60
	CV	27.89	32.86	16.73	40.01	22.88	33.25	40.98	48.13	31.04	30.24
	AST	BL	24h	48h	72h	5d	8d	11d	14d	17d	21d
Control	Mean	34.17^a	253.50^a	327.00^a	207.92^a	196.67^a	132.00^a	107.40^a	53.00^a	65.20^a	47.60^a
	Std. Dev.	13.35	106.53	89.92	65.03	122.53	53.70	26.93	13.75	35.80	7.09
	CV	39.08	42.02	27.50	31.28	62.30	40.68	25.08	25.94	54.91	14.90
EEB 400mg/Kg	Mean	36.75^a	145.50^a	202.17^a	163.33^a	111.07^a	83.72^a	72.00^a	59.00^a	53.58^a	53.83^a
	Std. Dev.	12.11	55.50	59.52	48.36	22.86	29.78	20.78	22.10	12.94	14.69
	CV	32.94	38.14	29.44	29.61	20.58	35.57	28.87	37.46	24.15	27.29
EEB 100mg/Kg	Mean	35.00^a	148.67^a	252.67^a	155.00^a	114.17^a	77.83^a	91.17^a	78.00^a	74.05^a	49.00^a
	Std. Dev.	15.95	66.43	77.15	47.08	32.52	27.68	37.71	24.86	25.79	18.09
	CV	45.57	44.68	30.54	30.38	28.49	35.56	41.37	31.87	34.83	36.92
Silymarin	Mean	31.92^a	224.17^a	254.50^a	181.37^a	114.67^a	94.33^a	83.92^a	75.83^a	58.25^a	57.67^a
	Std. Dev.	7.41	63.81	32.20	27.21	43.48	36.27	28.40	19.65	37.41	31.36
	CV	23.20	28.47	12.65	15.00	37.92	38.45	33.84	25.91	64.22	54.38
	ALP	BL	24h	48h	72h	5d	8d	11d	14d	17d	21d
Control	Mean	24.67^a	216.17^a	246.17^a	172.00^a	167.00^a	99.00^a	79.60^a	66.80^a	41.80^a	37.80^a
	Std. Dev.	6.98	118.67	151.16	123.91	115.31	56.86	64.46	44.21	25.16	30.58
	CV	28.28	54.90	61.41	72.04	69.05	57.43	80.98	66.19	60.20	80.90
EEB 400mg/Kg	Mean	27.17^a	185.00^a	174.83^a	125.00^a	99.00^a	60.83^a	60.17^a	47.83^a	36.33^a	32.00^a
	Std. Dev.	8.13	79.80	76.94	93.23	93.29	44.67	43.74	28.73	13.75	13.19
	CV	29.92	43.14	44.01	74.58	94.23	73.44	72.70	60.06	37.84	41.22
EEB 100mg/Kg	Mean	21.33^a	174.17^a	235.67^a	134.00^a	114.50^a	67.17^a	52.50^a	36.67^a	41.17^a	28.83^a
	Std. Dev.	4.14	46.47	102.21	39.92	49.07	38.50	17.95	7.99	16.93	8.54
	CV	19.42	26.68	43.37	29.79	42.85	57.32	34.20	21.80	41.12	29.63
Silymarin	Mean	28.92^a	237.00^a	176.17^a	143.33^a	95.50^a	92.17^a	62.67^a	49.33^a	42.00^a	30.00^a
	Std. Dev.	8.05	86.21	74.04	74.93	56.79	71.45	19.22	16.08	14.32	9.59
	CV	27.85	36.38	42.03	52.28	59.47	77.52	30.67	32.60	34.11	31.97
	GGT	BL	24h	48h	72h	5d	8d	11d	14d	17d	21d
Control	Mean	6.38^a	11.90^a	12.75^a	8.50^a	9.35^a	6.12^a	9.24^a	6.12^a	6.12^b	8.16^a
	Std. Dev.	0.00	4.16	2.79	4.16	3.84	2.28	4.29	2.28	2.28	2.79
	CV	0.00	34.99	21.91	48.99	41.06	37.27	46.40	37.27	37.27	34.23
EEB 400mg/Kg	Mean	5.95^a	11.05^a	11.90^a	8.50^a	7.65^a	9.35^a	6.80^a	6.80^a	6.80^b	6.80^a
	Std. Dev.	0.66	3.84	2.63	2.63	2.79	3.84	2.63	2.63	2.63	2.63
	CV	11.07	34.74	22.13	30.98	36.51	41.06	38.73	38.73	38.73	38.73
EEB 100mg/Kg	Mean	5.95’^a	9.35^a	11.05^a	11.05^a	9.35^a	8.50^a	7.65^a	5.95^a	5.95^b	5.95^a
	Std. Dev.	0.66	2.08	3.84	3.84	2.08	4.16	4.27	2.08	2.08	2.08
	CV	11.07	22.27	34.74	34.74	22.27	48.99	55.78	34.99	34.99	34.99
Silymarin	Mean	6.38^a	8.50^a	12.75^a	11.90^a	7.65^a	9.35^a	8.50^a	9.35^a	6.20^a	8.50^a
	Std. Dev.	1.40	4.16	2.79	2.63	2.79	3.84	2.63	2.08	0.00	4.16
	CV	21.91	48.99	21.91	22.13	36.51	41.06	30.98	22.27	0.00	48.99

Table 2 Mean values of direct bilirubin (directBB), total bilirubin (totalBB), total proteins (TP), globulin albumins and total cholesterol of dogs (n=6) treated for 21 days with starch (negative control), dry extract of Bidens pilosa L. (Asteraceae) (EEB) (100 and 400mg/Kg) and Silymarin (30mg/Kg) after oral administration of CCL₄ (2.5mL/Kg), Goiânia, Goiás, Brazil

	totalBB	BL*	24h	48h	72h	5d	8d	11d	14d	17d	21d
Control	Mean	0.72^a	1.06^a	1.08^a	1.20^a	1.27^a	1.06^a	1.18^b	0.97^a	1.02^a	1.00^a
	Std. Dev.	0.15	0.17	0.12	0.42	0.46	0.17	0.15	0.24	0.19	0.20
	CV	20.47	16.43	10.85	34.96	36.58	15.79	12.57	24.76	18.22	20.29
EEB 400mg/Kg	Mean	0.62^a	1.04^a	0.97^a	0.94^a	0.94^a	0.86^a	0.88^a	0.83^a	0.82^a	0.87^a
	Std. Dev.	0.04	0.10	0.16	0.20	0.12	0.12	0.23	0.20	0.21	0.24
	CV	6.58	9.48	16.91	21.53	12.84	14.31	26.23	24.17	25.44	28.26
EEB 100mg/Kg	Mean	0.73^a	0.88^a	0.89^a	0.98^a	0.80^a	0.91^a	0.90^b	0.89^a	0.87^a	0.79^a
	Std. Dev.	0.15	0.16	0.19	0.12	0.14	0.10	0.10	0.09	0.12	0.24
	CV	20.99	17.90	20.87	11.89	17.68	11.10	11.58	10.29	13.58	29.97
Silymarin	Mean	0.68^a	1.07^a	1.00^a	0.99^a	0.82^a	0.94^a	0.90^b	0.82^a	0.82^a	0.80^a
	Std. Dev.	0.17	0.18	0.15	0.08	0.28	0.18	0.17	0.18	0.16	0.14
	CV	25.44	16.53	14.52	8.28	34.12	18.81	18.59	22.54	19.62	16.93
	directBB	BL	24h	48h	72h	5d	8d	11d	14d	17d	21d
Control	Mean	0.19^a	0.60^a	0.36^a	0.40^a	0.30^a	0.32^a	0.38^a	0.35^a	0.39^a	0.36^a
	Std. Dev.	0.07	0.25	0.08	0.12	0.31	0.10	0.05	0.12	0.11	0.03
	CV	35.92	41.49	23.40	30.89	0.30	30.91	12.46	34.39	27.96	9.02
EEB 400mg/Kg	Mean	0.20^a	0.37^a	0.31^a	0.35^a	0.30^a	0.27^a	0.25^b	0.32^a	0.29^a	0.31^a
	Std. Dev.	0.07	0.09	0.03	0.07	0.05	0.06	0.07	0.10	0.11	0.08
	CV	37.52	24.33	8.71	21.25	17.79	23.66	29.75	32.27	36.69	25.88
EEB 100mg/Kg	Mean	0.17^a	0.47^a	0.33^a	0.33^a	0.32^a	0.31^a	0.32^a	0.38^a	0.39^a	0.36^a
	Std. Dev.	0.08	0.08	0.06	0.07	0.05	0.05	0.04	0.08	0.10	0.07
	CV	45.52	16.55	18.30	21.83	16.55	17.81	12.81	21.96	25.07	18.79
Silymarin	Mean	0.21^a	0.43^a	0.35^a	0.34^a	0.48^a	0.33^a	0.33^a	0.33^a	0.28^a	0.28^a
	Std. Dev.	0.07	0.19	0.05	0.09	0.24	0.29	0.08	0.06	0.05	0.05
	CV	35.21	44.59	15.55	27.02	50.74	88.63	23.39	17.60	19.16	16.75
	TP	BL	24h	48h	72h	5d	8d	11d	14d	17d	21d
Control	Mean	6.48^a	7.22^a	7.03^a	7.43^a	7.53^a	7.74^a	7.44^a	7.38^a	7.90^a	7.50^a
	Std. Dev.	0.48	0.92	0.68	0.85	0.86	0.53	0.44	1.00	0.62	0.72
	CV	7.46	12.71	9.63	11.47	11.47	6.87	5.90	13.50	7.85	9.66
EEB 400mg/Kg	Mean	6.75^a	6.72^a	6.42^a	6.85^a	7.22^a	7.00^a	7.08^a	7.07^a	7.23^a	7.30^a
	Std. Dev.	0.38	0.81	0.50	0.69	0.97	0.50	0.60	0.73	0.48	0.51
	CV	5.68	12.00	7.85	10.15	13.39	7.11	8.54	10.31	6.58	6.93
EEB 100mg/Kg	Mean	6.77^a	7.03^a	7.02^a	7.18^a	7.32^a	7.38^a	7.55^a	7.52^a	7.63^a	8.03^a
	Std. Dev.	0.49	0.94	1.02	0.66	0.81	1.02	0.55	0.89	1.06	0.46
	CV	7.28	13.33	14.55	9.13	11.08	13.80	7.24	11.82	13.93	5.71
Silymarin	Mean	6.15^a	6.35^a	6.37^a	6.95^a	7.37^a	6.88^a	6.90^a	6.82^a	6.97^a	6.83^a
	Std. Dev.	0.53	0.48	0.94	0.46	0.94	0.60	0.27	0.44	0.84	0.75
	CV	8.65	7.50	14.82	6.61	12.78	8.74	3.89	6.39	12.07	10.98
	Albumin	BL	24h	48h	72h	5d	8d	11d	14d	17d	21d
Control	Mean	2.88^a	2.75^a	3.23^a	3.05^a	2.68^a	2.81^a	2.99^a	3.04^a	2.98^a	2.51^a
	Std. Dev.	0.26	0.54	0.76	0.27	0.34	0.47	0.58	0.38	0.37	0.31
	CV	9.05	19.58	23.51	8.94	12.77	16.60	19.25	12.41	12.52	12.37
EEB 400mg/Kg	Mean	3.09^a	2.82^a	2.92^a	3.36^a	2.79^a	3.05^a	2.69^a	2.77^a	2.99^a	2.98^a
	Std. Dev.	0.30	0.46	0.71	0.56	0.18	0.32	0.39	0.51	0.36	0.25
	CV	9.73	16.26	24.44	16.55	6.45	10.66	14.52	18.41	12.12	8.56
EEB 100mg/Kg	Mean	3.00^a	3.18^a	3.46^a	3.04^a	3.16^a	3.07^a	2.68^a	2.99^a	2.97^a	3.05^a
	Std. Dev.	0.23	0.31	1.10	0.33	0.50	0.51	0.26	0.32	0.37	0.33
	CV	7.52	9.72	31.84	10.69	15.77	16.70	9.87	10.59	12.61	10.84
Silymarin	Mean	2.77^a	2.65^a	3.16^a	2.90^a	2.97^a	2.94^a	3.05^a	3.22^a	3.02^a	2.86^a
	Std. Dev.	0.25	0.40	1.44	0.34	0.38	0.23	0.49	0.35	0.48	0.23
	CV	8.88	15.28	45.64	11.60	12.76	7.66	16.09	10.84	16.04	8.20
	Globulins	BL	24h	48h	72h	5d	8d	11d	14d	17d	21d
Control	Mean	3.60^a	4.46^a	3.81^a	4.39^a	4.85^a	4.11^a	3.71^a	3.62^a	4.10^a	4.16^a
	Std. Dev.	0.52	1.41	0.90	0.86	1.08	2.05	1.94	1.87	2.18	2.22
	CV	14.39	31.56	23.61	19.62	22.27	49.94	52.30	51.82	53.19	53.39
CV	5.95	25.31	23.76	29.68	19.12	17.21	22.03	15.22	11.38	10.06
EEB 100mg/Kg	Mean	3.77^a	3.86^a	3.56^a	4.14^a	4.16^a	4.31^a	4.88^a	4.53^a	4.67^a	4.98^a
	Std. Dev.	0.39	0.71	1.72	0.71	1.09	0.72	0.57	1.06	1.23	0.66
	CV	10.39	18.47	48.35	17.15	26.28	16.65	11.63	23.33	26.38	13.18
Silymarin	Mean	3.38^a	3.71^a	3.21^a	4.05^a	4.40^a	3.94^a	3.85^a	3.60^a	3.95^a	3.97^a
	Std. Dev.	0.65	0.80	2.00	0.65	0.79	0.52	0.52	0.75	0.93	0.81
	CV	19.26	21.72	62.21	15.99	17.87	13.12	13.58	20.74	23.56	20.46
	Cholesterol	BL	24h	48h	72h	5d	8d	11d	14d	17d	21d
Control	Mean	170.25^a	200.17^a	147.17^a	183.50^a	208.67^a	185.20^a	223.80^a	244.00^a	248.00^a	211.20^a
	Std. Dev.	25.03	52.83	27.92	49.71	66.96	24.17	65.49	32.76	53.61	32.81
	CV	14.70	26.39	18.97	27.09	32.09	13.05	29.26	13.42	21.62	15.54
EEB 400mg/Kg	Mean	175.00^a	176.83^a	161.33^a	195.00^a	210.00^a	206.00^a	233.17^a	217.67^a	220.83^a	196.00^a
	Std. Dev.	32.78	59.17	31.95	13.51	84.10	56.59	46.01	46.31	64.66	39.31
	CV	18.73	33.46	19.80	6.93	40.05	27.47	19.73	21.27	29.28	20.06
EEB 100mg/Kg	Mean	186.67^a	196.17^a	175.67^a	207.17^a	244.17^a	253.67^a	221.33^a	192.83^a	213.00^a	210.33^a
	Std. Dev.	24.71	71.41	37.56	59.23	88.60	142.97	36.19	46.15	74.73	53.85
	CV	13.24	36.40	21.38	28.59	36.29	56.36	16.35	23.93	35.09	25.60
Silymarin	Mean	186.58^a	168.17^a	199.17^a	196.67^a	193.17^a	157.50^a	208.17^a	257.00^a	236.83^a	203.00^a
	Std. Dev.	36.15	49.29	69.68	56.82	68.10	62.45	52.88	54.71	45.76	71.62
	CV	19.37	29.31	34.99	28.89	35.26	39.65	25.40	21.29	19.32	35.28

BL - Base Line. Equal letters in the same column do not differ between themselves (ANOVA and t. Test, P<0.05).

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Universidade Federal de Minas Gerais, Escola de Veterinária Caixa Postal 567, 30123-970 Belo Horizonte MG - Brazil, Tel.: (55 31) 3409-2041, Tel.: (55 31) 3409-2042 - Belo Horizonte - MG - Brazil
E-mail: abmvz.artigo@gmail.com

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Bidens pilosa L. (Asteraceae) cultivated in Brazil on acute liver disease in dogs

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