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Galanin receptors activation modulates myocardial metabolic and antioxidant responses to ischaemia/reperfusion stress
Author(s) -
Studneva Irina,
Serebryakova Larisa,
Veselova Oksana,
Pal'keeva Marina,
Molokoedov Alexander,
Ovchinnikov Michael,
Konovalova Galina,
Lankin Vadim,
Sidorova Maria,
Pisarenko Oleg
Publication year - 2019
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13164
Subject(s) - superoxide dismutase , galanin , glutathione peroxidase , oxidative stress , lipid peroxidation , chemistry , lactate dehydrogenase , reperfusion injury , medicine , antioxidant , creatine , endocrinology , pharmacology , ischemia , creatine kinase , receptor , biochemistry , neuropeptide , enzyme
The mechanisms of protective action of the neuropeptide galanin and its N‐terminal fragments against myocardial ischaemia/reperfusion (I/R) injury remain obscure. The aim of this work was to study effects of a novel peptide agonist of galanin receptors [βAla14, His15]‐galanin (2‐15) (G1) and the full‐length galanin (G2) on energy and antioxidant status of the heart with acute infarction. The peptides were synthesized by the automatic solid phase method using Fmoc technology. Their structure was identified by 1 H‐ NMR spectroscopy and MALDI ‐ TOF mass spectrometry. Experiments were performed on anaesthetized open‐chest rats subjected to myocardial regional ischaemia and reperfusion. Intravenous (iv) administration of optimal doses of peptides G1 and G2 (1.0 and 0.5 mg/kg, respectively, at the onset of reperfusion significantly reduced infarct size (on average by 40% compared with control) and the plasma activity of creatine kinase‐ MB ( CK ‐ MB ) and lactate dehydrogenase ( LDH ). These effects were associated with augmented preservation of aerobic energy metabolism, increased activity of Cu,Zn superoxide dismutase (Cu,Zn‐ SOD ), catalase ( CAT ) and glutathione peroxidase ( GSH ‐Px) and decreased lipid peroxidation in the area at risk ( AAR ) at the end of reperfusion. Peptide G1 showed more efficient recovery of the majority of metabolic and antioxidant parameters. The results provide evidence that the galaninergic system can be considered a promising target to reduce energy dysregulation and oxidative damage in myocardial I/R injury.