Exogenous Galanin Reduces Hyperglycemia and Myocardial Metabolic Disorders Induced by Streptozotocin in Rats

The neuropeptide galanin (G) and its N-terminal fragments reduce the formation of reactive oxygen species and normalize myocardial metabolic and antioxidant state in experimental cardiomyopathy and ischemia/reperfusion injury. This study intends to elucidate the cardioprotective effect of G in rats treated with streptozotocin (STZ). The rat galanin (GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2) was prepared by the solid phase peptide synthesis using the Fmoc-strategy and purified by preparative HPLC. Its chemical structure was identified by 1 H-NMR spectroscopy and MALDI-TOF mass spectrometry. The animals were divided in four groups: C—normal control; S—STZ control, a single i.p. injection of STZ (35 mg/kg); SG—a single i.p. injection of STZ (35 mg/kg) and i.p. injections of G (5 nmol/kg/day for 4 weeks); and G—normal animals treated with G (5 nmol/kg/day for 4 weeks). Treatment with G prevented hyperglycemia in STZ rats. G significantly improved maximal ADP-stimulated respiration and respiratory control ratio in saponin-skinned myocardial fibers in SG group compared to S group. G enhanced myocardial metabolic state in animals treated with STZ by reducing ATP, phosphocreatine (PCr) and total creatine (ΣCr = PCr + Cr) losses, and decreasing lactate accumulation in parallel with elevation of glucose level. Administration of G reduced the increased activity of creatine kinase-MB and lactate dehydrogenase in blood plasma of STZ-treated rats. G also prevented the formation of STZ-induced lipid peroxidation products, thiobarbituric acid reactive substances, in blood plasma to a value not different from baseline. The results suggest that G may be a promising tool for reducing myocardial metabolic disorders in diabetes mellitus.