Streptozotocin-induced diabetic cardiomyopathy in rats: ameliorative effect of PIPERINE via Bcl2, Bax/Bcl2, and caspase-3 pathways.

Abstract

The objective of present investigation was to appraise the effects of piperine on STZ-induced diabetic cardiomyopathy in rats. Diabetes was induced in Sprague-Dawley rats with intraperitoneal STZ injection, and the rats were assigned to seven groups. Electrocardiograph, hemodynamic, various biochemical, molecular, and histological parameters were examined. Treatment with piperine significantly (p <0.05) restored altered myocardial functions, inhibited cardiac marker, and restored electrocardiogram and hemodynamic alterations. The elevated level of cardiac oxido-nitrosative stress and decreased cardiac Na-K-ATPase concentration, after STZ administration, were significantly (p <0.05) attenuated by piperine treatment. Piperine also considerably (p <0.05) increased myocardial mitochondrial enzyme activity. STZ-induced alteration in heart ANP, BNP, cTn-I, Bcl2, Bax/Bcl2, and caspase3 mRNA expression was significantly (p <0.05) restored by piperine treatment. Piperine administration reduced histopathological aberrations induced by STZ. In conclusion, the present investigation suggests that piperine ameliorates STZ-induced diabetic cardiomyopathy via modulation of caspase-3, Bcl2, Bax/Bcl2 pathways. Abbreviations: ACE: Angiotensin-Converting Enzyme; ANOVA: Analysis of Variance; ANP: Atrial Natriuretic Peptide; APAF: Apoptotic Protease-Activating Factor; ARB: Angiotensin Receptor Blockers; ATP: Adenosine Triphosphate; Bax: Bcl-2-associated X protein; Bcl2: B-cell lymphoma 2; BPM: Beats Per Minute; BNP: brain natriuretic peptide; CAD: Caspase-3-Activated DNase; cDNA: Complementary DNA; CK-MB: Creatine Kinase-MB; CPCSEA: Committee for the Purpose of Control And Supervision of Experiments on Animals; cTn-I: cardiac troponin I; DBP: Diastolic Blood Pressure; DCM: Diabetic Cardiomyopathy; DNA: Deoxyribonucleic Acid; DPX: DisterenePhthalate Xylene; ECG: Electrocardiogram; ETC: Electron Transport Chain; GOD-POD: Glucose Oxidase Peroxidase; GSH: Glutathione; IAEC: Institutional Animal Ethics Committee; IL-6: Interleukin-6; IL-1b: Interleukin-1b; LDH: Lactate Dehydrogenase; LV: Left Ventricle; LVEDP: left ventricular end-diastolic Pressure; MABP: Mean Arterial Blood Pressure; MDA: Malondialdehyde; mRNA: Messenger Ribonucleic Acid; MTT: 3- (4,5-Dimethylthiazol-2-yl)-2,5-DiphenyltetrazoliumBromide; NADH: Nicotinamide Adenine Dinucleotide Phosphate; NADPH: Nicotinamide Adenine Dinucleotide Phosphate Hydrogen; NO: nitric oxide; NP: Natriuretic Peptides; OXPHOS: Oxidative Phosphorylation; p.o.: per os; PCR: Polymerase Chain Reaction; RT-PCR: Reverse Transcriptionpolymerase Chain Reaction; PPAR: Peroxisome Proliferator-Activated Receptor Gamma; RAS: Renin-Angiotensin System; RNA: Ribonucleic Acid; ROS: Reactive Oxygen Species; SBP: Systolic Blood Pressure; SDH: Succinate Dehydrogenase; SEM: Standard Error Means; SOD: superoxide dismutase: STZ: Streptozotocin; TNF: Tumor Necrosis Factor Alpha; TnI: Troponin I.