Galanin and its N-terminal fragments reduce acute myocardial infarction in rats

Add time:08/21/2019    Source:sciencedirect.com

Agonists and antagonists for galanin receptor subtypes GalR1-3 can be used as putative therapeutics targets for the treatment of various human diseases. However, effects of galanin and its N-terminal fragments on myocardial ischemia/reperfusion injury remain unclear. This study was designed to assess the ability of the full-length galanin (GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2, G1), the natural fragments WTLNSAGYLL-NH2 (G2) and WTLNSAGYLLGPHA (G3), and their modified analogs WTLNAAGYLL (G4) and WTLNSAGYLLGPβAH (G5) to limit acute myocardial infarction in rats in vivo. The peptides G2-5 were synthesized by the automatic solid phase method using Fmoc technology, purified by preparative HPLC and identified by 1H NMR spectroscopy and MALDI −TOF mass spectrometry. The peptides G1-5 were administered by i.v. bolus injection at the onset of reperfusion at doses of 0.25, 0.50, 1.0, 2.0 or 3.0 mg/kg. The optimal doses of the peptides G1-5 significantly reduced the infarction area and decreased the activity of CK-MB and LDH in blood plasma at the end of reperfusion compared with the control. Among the peptides studied, G5 showed high efficacy in reducing the infarct size and the activity of necrosis markers in blood plasma with no significant effect on hemodynamic parameters. The results suggest that a novel agonist for galanin receptors G5 may be a promising tool for the treatment of myocardial ischemia/reperfusion (I/R) injury. Further studies are warranted to explore the stability of this peptide in blood plasma and mechanisms that contribute to its cardioprotective effects.

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