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Brazilian Journal of Cardiovascular Surgery

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ORIGINAL ARTICLE • Braz. J. Cardiovasc. Surg. 38 (04) • 2023 • https://doi.org/10.21470/1678-9741-2022-0251 copy

Protective Effects of Fuziline on Dobutamine-Induced Heart Damage in Mice

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Introduction:

Fuziline is one of the many antioxidants currently being tested to treat cardiac damage. In our study, histopathological and biochemical effects of fuziline were investigated in mice with dobutamine-induced heart damage in vitro.

Methods:

Thirty-two adult male BALB/c mice, average weight of 18-20 g, were randomly divided into four groups - Group 1 (sham, n=8), Group 2 (control, dobutamine, n=8), Group 3 (treatment 1, dobutamine + fuziline, n=8), and Group 4 (treatment 2, fuziline, n=8). Biochemical parameters and total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) values were measured. Interleukin 1 beta (IL-1β), NLR family, pyrin domain containing protein 3 (NLRP3), 8-hydroxy-deoxyguanosine (8-OHDG), gasdermin D (GSDMD), and galectin 3 (GAL-3) levels were analyzed by enzyme-linked immunosorbent assay method, and histopathological examination of heart tissues was performed.

Results:

When dobutamine + fuziline and fuziline groups were compared, troponin-I (P<0.05), NLRP3 (P<0.001), GSDMD (P<0.001), 8-OHDG (P<0.001), IL-1β (P<0.001), and GAL-3 (P<0.05) were found to be statistically significant. TOS level was the highest in the dobutamine group (P<0.001) and TAS level was the highest in the fuziline group (P<0.001). OSI level was statistically significant between the groups (P<0.001). In histopathological examination, focal necrosis areas were smaller in the dobutamine + fuziline group than in the dobutamine group, and cardiac myocytes were better preserved.

Conclusion:

Fuziline markedly reduced cardiac damage and pyroptosis in mice with dobutamine-induced heart damage by lowering the levels of GSDMD, 8-OHDG, IL-1β, and GAL-3. It also prevented necrosis of cardiac myocytes in histopathological evaluation.

Abbreviations, Acronyms & Symbols
8-OHDG	= 8-hydroxy-deoxyguanosine		ISO	= Isoproterenol
ALT	= Alanine aminotransferase		K	= Potassium
AU	= Arbitrary units		MI	= Myocardial infarction
Cr	= Creatinine		Na	= Sodium
CVD	= Cardiovascular disease		NLRP3	= NLR family, pyrin domain containing protein 3
DNA	= Deoxyribonucleic acid		OSI	= Oxidative stress index
ECG	= Electrocardiogram		PM2.5	= Particulate matter 2.5
GAL-3	= Galectin 3		ProBNP	= Pro-brain natriuretic peptide
GSDMD	= Gasdermin D		RNS	= Reactive nitrogen species
HF	= Heart failure		ROS	= Reactive oxygen species
IL-1β	= Interleukin 1 beta		SD	= Standard deviation
IL-18	= Interleukin 18		TAS	= Total antioxidant status
IP	= Intraperitoneally		TOS	= Total oxidant status

Groups	Weight	Gender	Genus	N=32 piece
Group 1 (sham)	18-20 g	Male	BALB/c mice	8
Group 2 (control, dobutamine)	18-20 g	Male	BALB/c mice	8
Group 3 (treatment 1, dobutamine + fuziline)	18-20 g	Male	BALB/c mice	8
Group 4 (treatment 2, fuziline)	18-20 g	Male	BALB/c mice	8

	Sham			Dobutamine			Fuziline			Dobutamine + Fuziline
	Min.	Max.	SD	Min.	Max.	SD	Min.	Max.	SD	Min.	Max.	SD	P-value^a a Analysis of variance test,
Pro-BNP (ng/l)	40.00	67.00	56.89 ± 8.71	49	69.9	60.93 ± 7.64	51.01	62.4	56.73 ± 4.67	59	69.99	65.37 ± 4,13	0.051
Urea (mg/dl)	11.96	26.90	19.72 ± 5.02	10.7	20.03	15.88 ± 2.99	10.7	25	16.99 ± 5.33	10	34.68	23.15 ± 9.21	0.109
Creatinine (mg/dl)	0.15	0.50	0.34 ± 0.13	0.16	0.9	0.52 ± 0.23	0.64	0.99	0.83 ± 0.12	0.1	0.61	0.34 ± 0.21	0.001^ P<0.001
ALT (U/l)	20.00	130.00	67.38 ± 35.64	10	65	40.63 ± 22.22	13	85	45.57 ± 30.46	17	99	46.25 ± 27.23	0.291
Sodium (mmol/l)	159.00	164.00	160.88 ± 1.81	159	163	161 ± 1.31	160	163	161.71 ± 1.11	159	168	162.38 ± 2.62	0.345
Potassium (mmol/l)	3.40	4.10	3.74 ± 0.26	3.5	4.1	3.75 ± 0.17	3.3	4.4	3.71 ± 0.36	3.2	3.9	3.65 ± 0.23	0.872
Troponin-I (pg/ml)	2276.85	9919.89	5046 ± 2306	2424.7	13518.08	6775 ± 4182	3211.77	5970.83	4435 ± 1000	4365.06	13677.76	8967 ± 3174	0.025^* * P<0.05,

	Sham			Dobutamine			Fuziline			Dobutamine + Fuziline
	Min.	Max.	SD	Min.	Max.	SD	Min.	Max.	SD	Min.	Max.	SD	P-value^a a Analysis of variance test,
NLRP3 (ng/ml)	1.43	2.04	1.68 ± 0.2	0.973	1.422	1.17 ± 0.15	1.397	2.102	1.64 ± 0.27	1.44	1.908	1.71 ± 0.15	0.001^ P<0.001
GSDMD (ng/l)	256.30	428.58	341.14 ± 60.01	503.362	750.2	588.91 ± 80.22	140.492	153.591	145.27 ± 5.36	140.201	599.628	431.94 ± 145.05	0.001^ P<0.001
8-OHDG (ng/ml)	1.15	1.54	1.32 ± 0.12	1.238	2.952	2.37 ± 0.5	1.149	1.552	1.35 ± 0.15	1.03	1.813	1.37 ± 0.24	0.001^ P<0.001
IL-1β (pg/ml)	422.03	824.23	569.32 ± 124.79	817.291	1.388.563	1012.32 ± 187.83	431.356	823.101	559.83 ± 133.21	428.42	850.3	713.23 ± 137.24	0.001^ P<0.001
GAL-3 (ng/ml)	0.75	2.94	1.28 ± 0.72	1.411	2.948	2.05 ± 0.53	0.823	1.556	1.04 ± 0.27	0.886	1.715	1.46 ± 0.28	0.004^* * P<0.05,
TOS (μmol H2O2 equivalent/l)	7.20	13.10	10.1 ± 2.08	11.3	16.2	14.6 ± 1.66	9.52	12.1	10.67 ± 0.87	11.2	14.2	13.06 ± 1.01	0.001^ P<0.001
TAS (mmol Trolox equivalent/l)	1.20	2.30	1.88 ± 0.34	0.66	1.09	0.87 ± 0.15	1.96	2.6	2.19 ± 0.25	1.69	1.92	1.79 ± 0.08	0.001^ P<0.001
OSI (AU)	0.35	0.88	0.57 ± 0.19	1.11	2.3	1.74 ± 0.41	0.38	0.58	0.49 ± 0.08	0.59	0.82	0.73 ± 0.07	0.001^ P<0.001

		NLRP3	GSDMD	8-OHDG	IL-1β	GAL-3	TOS	TAS	OSI
NLRP3 (ng/ml)	r	1.00	-.503^ P<0.001	-.607^ P<0.001	-0.33	-0.18	-.367^* * P<0.05,	.663^ P<0.001	-.656^ P<0.001
NLRP3 (ng/ml)	P-value		0.001	0.001	0.07	0.34	0.04	0.001	0.001
GSDMD (ng/L)	r	-.503^ P<0.001	1.00	.510^ P<0.001	.634^ P<0.001	.506^ P<0.001	.609^ P<0.001	-.748^ P<0.001	.669^ P<0.001
GSDMD (ng/L)	P-value	0.001		0.001	0.001	0.001	0.001	0.001	0.001
8-OHDG (ng/ml)	r	-.607^ P<0.001	.510^ P<0.001	1.00	.722^ P<0.001	.559^ P<0.001	.578^ P<0.001	-.759^ P<0.001	.773^ P<0.001
8-OHDG (ng/ml)	P-value	0.001	0.001		0.001	0.001	0.001	0.001	0.001
IL-1β (pg/ml)	r	-0.33	.634^ P<0.001	.722^ P<0.001	1.00	.865^ P<0.001	.735^ P<0.001	-.739^ P<0.001	.796^ P<0.001
IL-1β (pg/ml)	P-value	0.07	0.001	0.001		0.001	0.001	0.001	0.001
GAL-3 (ng/ml)	r	-0.18	.506^ P<0.001	.559^ P<0.001	.865^ P<0.001	1.00	.689^ P<0.001	-.590^ P<0.001	.676^ P<0.001
GAL-3 (ng/ml)	P-value	0.34	0.001	0.001	0.001		0.001	0.001	0.001
TOS (μmol H2O2 equivalent/L)	r	-.367^* * P<0.05,	.609^ P<0.001	.578^ P<0.001	.735^ P<0.001	.689^ P<0.001	1.00	-.698^ P<0.001	.797^ P<0.001
TOS (μmol H2O2 equivalent/L)	P-value	0.04	0.001	0.001	0.001	0.001		0.001	0.001
TAS (mmol Trolox equivalent/L)	r	.663^ P<0.001	-.748^ P<0.001	-.759^ P<0.001	-.739^ P<0.001	-.590^ P<0.001	-.698^ P<0.001	1.00	-.928^ P<0.001
TAS (mmol Trolox equivalent/L)	P-value	0.001	0.001	0.001	0.001	0.001	0.001		0.001
OSI (AU)	r	-.656^ P<0.001	.669^ P<0.001	.773^ P<0.001	.796^ P<0.001	.676^ P<0.001	.797^ P<0.001	-.928^ P<0.001	1.00
OSI (AU)	P-value	0.001	0.001	0.001	0.001	0.001	0.001	0.001

	Dobutamine group (control)
	Area (mm²)	Necrosis (mm²)	%
1	4.83	0.34	7.00
2	4.60	0.28	6.00
3	5.29	0.26	5.00
4	5.06	0.40	8.00
5	5.52	0.39	7.00
6	5.52	0.30	5.50
7	5.06	0.25	5.00
Median (mm²)	5.13	0.32	6.21

	Dobutamine + fuziline group (treatment 1)
	Area (mm²)	Necrosis (mm²)	%
1	4.60	0.05	1.00
2	5.29	0.13	2.50
3	5.52	0.15	2.75
4	5.06	0.08	1.50
5	5.29	0.16	3.00
6	4.83	0.10	2.00
7	5.06	0.14	2.75
Median (mm²)	5.09	0.11	2.25

Authors’ Roles & Responsibilities
YH	Substantial contributions to the conception and design of the work; and the acquisition, analysis and interpretation of data for the work; drafting the work and revising it critically for important intellectual content; final approval of the version to be published
MSA	Substantial contributions to the acquisition, analysis and interpretation of data for the work; drafting the work and revising it; final approval of the version to be published
EKE	Substantial contributions to the acquisition, analysis and interpretation of data for the work; drafting the work and revising it; final approval of the version to be published
NK	Substantial contributions to the acquisition, analysis and interpretation of data for the work; drafting the work and revising it; final approval of the version to be published
İK	Substantial contributions to the conception and design of the work; revising it critically for important intellectual content; final approval of the version to be published
MEG	Substantial contributions to the conception and design of the work; revising it critically for important intellectual content; final approval of the version to be published
ET	Substantial contributions to the conception and design of the work; revising it critically for important intellectual content; final approval of the version to be published
RD	Substantial contributions to the conception and design of the work; revising it critically for important intellectual content; final approval of the version to be published
KE	Substantial contributions to the conception and design of the work; revising it critically for important intellectual content; final approval of the version to be published
YÇ	Substantial contributions to the conception and design of the work; revising it critically for important intellectual content; final approval of the version to be published
MP	Substantial contributions to the conception and design of the work; revising it critically for important intellectual content; final approval of the version to be published

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