Stilbenoid pterostilbene complexed with cyclodextrin preserves left ventricular function after myocardial infarction in rats: possible involvement of thiol proteins and modulation of phosphorylated GSK-3β.
Oxidative stress alters signalling pathways for survival and cell death favouring the adverse remodelling of postmyocardial remnant cardiomyocytes, promoting functional impairment. The administration of pterostilbene (PTS), a phytophenol with antioxidant potential, can promote cardioprotection and represents a therapeutic alternative in acute myocardial infarction (AMI). The present study aims to explore the effects of oral administration of PTS complexed with hydroxypropyl-β-cyclodextrin HPβCD (PTS:HPβCD complex) on the glutathione cycle, thiol protein activities and signalling pathways involving the protein kinase B (AKT) and glycogen synthase kinase-3β (GSK-3β) proteins in the left ventricle (LV) of infarcted rats. Animals were submitted to acute myocardial infarction through surgical ligation of the descending anterior branch of the left coronary artery and received over 8 days, by gavage, PTS:HPβCD complex at dose of 100 mg kg-1 day-1 (AMI + PTS group) or vehicle (aqueous solution with HPβCD) divided into Sham-operated (SHAM) and infarcted (AMI) groups. The results showed that the PBS: HPβCD complex decreased lipid peroxidation, prevented the decrease in thioredoxin reductase (TRxR) activity, and increased the activity of glutathione-S-transferase (GST) and glutaredoxin (GRx). Additionally, the expression of nuclear factor-erythroid two (Nrf2) and p-GSK-3β was increased, whereas the p-GSK-3β/GSK-3β ratio was reduced in the LV of the infarcted animals. Overall, the PTS:HPβCD complex modulates activity of thiol-dependent enzymes and induces to the expression of antioxidant proteins, improving systolic function and mitigating the adverse cardiac remodelling post infarction.
['Lacerda|Denise|D|http://orcid.org/0000-0001-6052-8884', 'Ortiz|Vanessa|V|', 'Türck|Patrick|P|http://orcid.org/0000-0001-5994-5218', 'Campos-Carraro|Cristina|C|', 'Zimmer|Alexsandra|A|', 'Teixeira|Rayane|R|', 'Bianchi|Sara|S|http://orcid.org/0000-0002-3759-6587', 'de Castro|Alexandre Luz|AL|', 'Schenkel|Paulo Cavalheiro|PC|http://orcid.org/0000-0002-7386-231X', 'Belló-Klein|Adriane|A|', 'Bassani|Valquiria Linck|VL|http://orcid.org/0000-0001-9525-5855', 'da Rosa Araujo|Alex Sander|AS|http://orcid.org/0000-0002-9482-7388']
D000818:Animals D000975:Antioxidants D017209:Apoptosis D002316:Cardiotonic Agents D003505:Cyclodextrins D004195:Disease Models, Animal D000071679:Glycogen Synthase Kinase 3 beta D006801:Humans D015227:Lipid Peroxidation D009203:Myocardial Infarction D032383:Myocytes, Cardiac D051267:NF-E2-Related Factor 2 D018384:Oxidative Stress D010766:Phosphorylation D051381:Rats D013267:Stilbenes D016277:Ventricular Function, Left
cyclodextrin Antioxidant cardioprotection heart failure natural products stilbene