L. Serebryakova, I. Studneva, A. Timoshin
May 24, 2021
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Influential Citations
4
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Journal
International Journal of Peptide Research and Therapeutics
Abstract
Natural and chemically modified N-terminal galanin fragments (WTLNSAGYLLGPHA-OH (G1) and WTLNSAGYLLGPβAH-OH (G2), respectively) reduce functional and metabolic disturbances in the heart during experimental ischemia and reperfusion. The aim of this work was to examine whether these peptides and full-length rat galanin (GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2, G3) decrease the formation of reactive oxygen species (ROS) and lipid peroxidation products in the heart with ischemia/reperfusion (I/R) injury. The peptides were synthesized by the automatic solid phase method using Fmoc technology. Their structure was identified by 1H-NMR spectroscopy and MALDI-TOF mass spectrometry. Experiments were performed on anaesthetized open-chest rats subjected to myocardial regional ischemia and reperfusion. The microdialysis method and the 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) spin trap were used to monitor ROS content in the area at risk (AAR). Intravenous administration of G1, G2 or G3 after occlusion of coronary artery significantly decreased the content of DMPO-OH spin adduct in interstitium of the AAR during reperfusion compared to the control. These effects were accompanied by limitation of infarct size, reduction of the plasma activity of creatine kinase-MB and lactate dehydrogenase, and better preservation of the energy state of the AAR. In addition, peptides G2 and G3 significantly reduced the formation of thiobarbituric acid reactive substances in the AAR. The overall protective action of the peptides decreased in the order G2 > G3 > G1. The results suggest that pharmacological agonists of galanin receptors can be considered as promising agents to reduce oxidative stress in myocardial I/R injury.