Effective inhibition of cardiomyocyte apoptosis through the combination of trimetazidine and N-acetylcysteine in a rat model of myocardial ischemia and reperfusion injury
| Autor: | Vahide Savci, Sinan Cavun, Berrin Avci, Aysun Yermezler, Zehra Serdar, Tunay Şentürk |
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| Přispěvatelé: | Uludağ Üniversitesi/Tıp Fakültesi/Kardiyoloji Anabilim Dalı., Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Farmakoloji Anabilim Dalı., Uludağ Üniversitesi/Tıp Fakültesi/Histoloji ve Embriyoloji Anabilim Dalı., Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyokimya Anabilim Dalı., Şentürk, Tunay, Çavun, Sinan, Avcı, Berrin, Yermezler, Aysun, Serdar, Zehra, Savcı, Vahide, ABE-6685-2020, AAC-9702-2019, C-1517-2017 |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Serum Cardiac & cardiovascular systems Unclassified drug medicine.medical_treatment Myocardial Ischemia Trimetazidine Blood Pressure Apoptosis Pharmacology Arrhythmias medicine.disease_cause Infarct size Animal tissue Acetylcysteine chemistry.chemical_compound Nitroglycerin Coronary risk Heart infarction size Malondialdehyde Free-fatty-acids Endothelial-cells Protein S100B Myocytes Cardiac Disease Saline TUNEL assay Experimental myocardial ischemia Cell Death Nick end labeling Caspase 3 Fatty Acids Malonaldehyde Heart Coronary Vessels Glutathione Immunohistochemistry Reperfusion injury Severtiy Anesthesia Left coronary artery Coronary artery ligation Heart Failure Ketone Bodies Cardiology and Cardiovascular Medicine Animal cell medicine.drug Sodium chloride Activation S100 Calcium Binding Protein beta Subunit Article Heart infarction prevention medicine Animals Animal model Animal experiment Rats Wistar m65 protein Inflammation business.industry Cytokeratin 18 Myocardium Heart muscle cell M30/M65 medicine.disease Monotherapy Nonhuman N-acetylcysteine Rats Oxygen Disease Models Animal Biological marker Glucose Cardiovascular system & cardiology chemistry Oxidative stress Peripheral vascular disease Rat Heart muscle reperfusion business Controlled study |
| Popis: | Objective: Apoptosis is the early and predominant form of cell death in infarcted myocardia. The aim of the study was to investigate the effects of trimetazidine (TMZ) and N-acetylcysteine (NAC), used alone or in combination, on oxidative stress, infarct size, and ischemia-reperfusion (IR)-induced cardiomyocyte apoptosis in a rat model of myocardial IR. Methods and results: Myocardial IR was established by ligating an area under the left main coronary artery for 30 min followed by 3 h of reperfusion. Saline (1 ml/kg), NAC (50, 150 mg/kg), or TMZ (3, 5 mg/kg) was intravenously injected during the middle of the ischemic period. At the end of the reperfusion, blood samples were collected from the animals to measure serum M30 and M65 levels, which are markers of cell death, the S100b level, which is a marker of inflammation, and the malondialdehyde (MDA) level, which is a marker of oxidative stress. The infarct size was evaluated as the ratio of the infarct area to the risk area. Apoptotic activation was assessed by caspase-3 immunostaining and a TUNEL assay. TMZ and NAC, either alone or in combination, significantly reduced serum MDA levels, infarct area and apoptotic activity compared to those observed in saline group. Interestingly, the infarct area was more smaller in TMZ (3 and 5 mg/kg) injected groups (9.72 +/- 1.3% and 9.96 +/- 2.3%) than those observed in NAC (50 and 150 mg/kg) (16.1 +/- 2.5% and 19.1 +/- 2.14%) or TMZ (5 mg/kg)- NAC (150 mg/kg) combination groups (16.9 +/- 1.6%). However, the apoptotic activity was reduced more significantly in the combination of TMZ (5 mg/kg)-NAC (50 mg/kg) compared to TMZ-only group. Neither TMZ or NAC treatments nor the combination of the drugs significantly affected serum M30, M65 and S100B levels. Conclusion: Intravenous NAC and TMZ administration decreased oxidative stress, infarct area and apoptotic activity in a rat model of IR. Although the combination treatment was more effective in reducing the apoptotic activity than either treatment groups alone, TMZ treatment was more successful in reducing the infarct area than NAC or combination treatments. Present results suggest that, in addition to mechanical attempts to secure myocardial reperfusion, the use of TMZ and NAC may help to reduce IR injury. |
| Databáze: | OpenAIRE |
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