The mechanisms of cardiac protection using a synthetic agonist of galanin receptors during chronic administration of doxorubicin

Figures

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  Fig. 1. Echocardiography variables and indices of oxidative stress and cell membrane damage in the studied groups. A – Left ventricular end-systolic diameter (LVESD). B – Fractional shortening (FS) was calculated as (LVEDD – LVESD)/ LVEDD × 100%, where LVEDD is the left ventricular end-diastolic diameter. C – Ejection fraction (EF) was calculated as (LVEDV – LVESV)/LVEDV × 100%, where LVEDV is the left ventricular diastolic volume and LVESV is the left ventricular systolic volume. D – Myocardial content of thiobarbituric acid reactive substances (TBARS). E – TBARS concentration in blood plasma. F – The plasma activity of creatine kinase-MB (CK-MB). IS – initial state; C – control; D – doxorubicin; D + G – doxorubicin + peptide G; G – peptide G. Values are expressed as the mean ± SEM for groups consisting of 12 animals each. P < 0.05 vs. *IS, #C, ^D, +D +G

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  Fig. 2. The effects of peptide G on histological changes in the hearts of rats treated with Dox. A – Control, HE, ×200. Slight plethora and erythrocyte stasis. B – Dox group, HBFP, ×200. Extensive fuchsinophilia of cardiomyocytes. C – D + G group, HBFP, ×200. Groups of single cardiomyocytes with cytoplasmic fuchsinophilia. D – G group, HBFP, ×200. Slight erythrocyte stasis, lack of fuchsinophilic cardiomyocytes

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  Fig. 3. Myocardial levels of glucose, lactate, glutamic acid (Glu), aspartic acid (Asp), alanine (Ala), and ammonia (NH4 +) in the studied groups after 8 weeks of experiment. C – control; D – doxorubicin; D + G – doxorubicin + peptide G; G – peptide G. Values are expressed as the mean ± SEM for groups consisting of 6 animals each. P < 0.05 vs. # C, ^D

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  Fig. 4. Intracellular signaling pathways activated by peptide G, a pharmacological galanin receptor agonist (adapted from Runesson [31]). AC – adenylate cyclase; (p)BAD – (phosphorylated) BCl-2 associated death promoter; CaCC – Ca2+-activated chloride channel; cAMP – 3’,5’-cyclic adenosine monophosphate; (p)CREB – (phosphorylated) cAMP response element binding protein; DAG – diacylglycerol; GIRK – G protein-coupled inwardly rectifying potassium channel; IP3 – inositol triphosphate; MAPK – mitogen- activated protein kinase; MEK – mitogen extracellular kinase; PDK-1 – phosphoinositide-dependent protein- kinase I; PIP2 –phosphatidylinositol biphosphate; PIP3 – phosphatidylinositol triphosphate; PI3K – phosphatidylinositol 3-kinase; PKB – protein kinase B; PLC – phospholipase C; RhoA – Ras homolog gene family, member A

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  Fig. 5. Galanin GalR2 receptor activation by peptide G reduces myocardial systolic dysfunction in Dox-induced CM thanks to an improved metabolic and antioxidant state of the heart