Sulforaphane effects on postinfarction cardiac remodeling in rats: modulation of redox-sensitive prosurvival and proapoptotic proteins.
This study investigated whether sulforaphane (SFN), a compound found in cruciferous vegetables, could attenuate the progression of post-myocardial infarction (MI) cardiac remodeling. Male Wistar rats (350 g) were allocated to four groups: SHAM (n=8), SHAM+SFN (n=7), MI (n=8) and MI+SFN (n=5). On the third day after surgery, cardiac function was assessed and SFN treatment (5 mg/kg/day) was started. At the end of 25 days of treatment, cardiac function was assessed and heart was collected to measure collagen content, oxidative stress and protein kinase. MI and MI+SFN groups presented cardiac dysfunction, without signs of congestion. Sulforaphane reduced fibrosis (2.1-fold) in infarcted rats, which was associated with a slight attenuation in the cardiac remodeling process. Both infarcted groups presented increases in the oxidative markers xanthine oxidase and 4-hydroxinonenal, as well as a parallel increase in the antioxidant enzymes glutathione peroxidase and superoxide dismutase. Moreover, sulforaphane stimulated the cytoprotective heme oxygenase-1 (HO-1) (38%). Oxidative markers correlated with ERK 1/2 activation. In the MI+SFN group, up-regulation of ERK 1/2 (34%) and Akt (35%), as well as down-regulation of p38 (52%), was observed. This change in the prosurvival kinase balance in the MI+SFN group was related to a down-regulation of apoptosis pathways (Bax/Bcl-2/caspase-3). Sulforaphane was unable to modulate autophagy. Taken together, sulforaphane increased HO-1, which may generate a redox environment in the cardiac tissue favorable to activation of prosurvival and deactivation of prodeath pathways. In conclusion, this natural compound contributes to attenuation of the fibrotic process, which may contribute to mitigation against the progression of cardiac remodeling postinfarction.
Laboratory of Cardiovascular Physiology, Institute of Basic Health Science, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Rafael Oliveira
RO
Fernandes
Laboratory of Cardiovascular Physiology, Institute of Basic Health Science, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Centro Universitário Ritter dos Reis (Uniritter), Porto Alegre, Rio Grande do Sul, Brazil.
Alexandre Luz
AL
De Castro
Laboratory of Cardiovascular Physiology, Institute of Basic Health Science, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Jéssica Hellen Poletto
JH
Bonetto
Laboratory of Cardiovascular Physiology, Institute of Basic Health Science, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Vanessa Duarte
VD
Ortiz
Laboratory of Cardiovascular Physiology, Institute of Basic Health Science, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Dalvana Daneliza
DD
Müller
Laboratory of Cardiovascular Physiology, Institute of Basic Health Science, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Cristina
C
Campos-Carraro
Laboratório de Histofisiologia Comparada, Departamento de Ciências Morfológicas, Instituto de Ciências Básicas da Saúde, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Silvia
S
Barbosa
Laboratório de Biologia Celular e Tecidual, Departamento de Ciências Morfofisiológicas, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Laura Tartari
LT
Neves
Laboratório de Biologia Celular e Tecidual, Departamento de Ciências Morfofisiológicas, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Léder Leal
LL
Xavier
Laboratory of Cardiovascular Physiology, Institute of Basic Health Science, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Paulo Cavalheiro
PC
Schenkel
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Pawan
P
Singal
Medical Sciences Division, Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada.
Neelam
N
Khaper
Laboratory of Cardiovascular Physiology, Institute of Basic Health Science, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Alex Sander
AS
da Rosa Araujo
Laboratory of Cardiovascular Physiology, Institute of Basic Health Science, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: belklein@ufrgs.br.
Adriane
A
Belló-Klein
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D005355:Fibrosis; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051547:Heme Oxygenase-1 / Q000737:chemistry / Q000378:metabolism; D007274:Injections, Intraperitoneal; D017879:Isothiocyanates / Q000008:administration & dosage / Q000627:therapeutic use*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D017208:Rats, Wistar; D013454:Sulfoxides; D020257:Ventricular Remodeling / Q000187:drug effects*
D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D017879:Isothiocyanates; D013454:Sulfoxides; D051547:Heme Oxygenase-1; C016766:sulforaphane
Autophagy; Heart failure; Heme oxygenase-1; Isothiocyanate; Myocardial infarction; Oxidative stress