Melatonin has cardioprotective effects in a rat model of cardiorenal syndrome. - GreenMedInfo Summary
The cardioprotective effect of melatonin and exendin-4 treatment in a rat model of cardiorenal syndrome.
J Pineal Res. 2016 Jul 28. Epub 2016 Jul 28. PMID: 27465663
We investigated the cardioprotective effect of melatonin (Mel) and exendin-4 (Ex4) treatment in a rat model of cardiorenal syndrome (CRS). Male-adult SD rats (n=48) were randomly and equally divided into sham-control (SC), dilated cardiomyopathy (DCM) (doxorubicin 7 mg/kg i.p. every five days/ 4 doses), CRS (defined as DCM + CKD) only, CRS-Mel (20 mg/kg/day), CRS-Ex4 (10μg/kg/day) and CRS-Mel-Ex4. In-vitro results showed protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein), DNA/mitochondrial-damaged (γ-H2AX/cytosolic cytochrome-C) and apoptotic (cleaved caspase-3/PARP) biomarkers, and senescence (β-galactosidase cells) were upregulated, whereasmitochondrial ATP level was decreased in doxorubicin/ p-Cresol-treated H9C2 cells that were revised by Mel and Ex4 treatments (all p<0.001). By day 60, LVEF was highest in SC and lowest in CRS, significantly lower in DCM than in other treatment groups, lower in CRS-Mel and CRS-Ex4 than in CRS-Mel-Ex4, and lower in CRS-Mel than in CRS-Ex4, whereas LV chamber size and histopathology score showed a pattern opposite to that of LVEF among all groups (all p<0.001). Plasma creatinine level was highest in CRS and lowest in SC, and progressively decreased from CRS-Mel, CRS-Ex4, CRS-Mel-Ex4 to DCM (p<0.0001). Protein expressions of inflammation (TNF-α/NF-κB/MMP-2/MMP-9/IL-1β), apoptosis/DNA-damage (Bax/c-caspase-3/c-PARP/γ-H2AX), fibrosis (Samd3/TGF-β), oxidative-stress (NOX-1/NOX-2/NOX-4/oxidized protein), cardiac-hypertrophy/pressure-overload (BNP/β-MHC), and cardiac integrity (Cx43/α-MHC) biomarkers in LV myocardium showed an oppositepattern compared to that of LVEF among all groups (all p<0.001). Fibrotic area, DNA-damage (γ-H2AX(+) /53BP1(+) CD90(+) /XRCC1(+) CD90(+) ), and inflammation (CD14(+) /CD68(+) ) biomarkers in LV myocardium displayed a pattern opposite to that of LVEF among all groups (all p<0.001). Combined melatonin and exendin-4 treatment suppressed CRS-induced deterioration of LVEF and LV remodeling. This article is protected by copyright. All rights reserved.