Lokesh K Bhatt1, Addepalli Veeranjaneyulu2. 1. Department of Pharmacology, Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, India. Electronic address: bhatt.lokesh@gmail.com. 2. Department of Pharmacology, School of Pharmacy and Technology Management, NMIMS University, Vile Parle (W), Mumbai, India.
Abstract
BACKGROUND AND AIMS: Diabetes is a risk factor for exacerbated outcome after acute myocardial infarction (AMI) and doubles the risk of mortality after MI. Increased levels of MMP-2 and MMP-9 in diabetes cause vascular remodelling, which leads to cardiovascular complications of diabetes. We hypothesized that inhibition of MMP-2 and MMP-9 can reduce worsening of myocardial ischemia in diabetic patients. Further, we hypothesized that minocycline induced MMP-2 and MMP-9 inhibition will be potentiated by aspirin and the combination of both drugs will prevent worsening of MI in diabetic patients. In the present study, efficacy of combination of minocycline and aspirin to attenuate exacerbation of myocardial ischemia/reperfusion (I/R) injury in diabetic rats was evaluated. METHODS: Diabetes was induced in male Wistar rats by streptozotocin (55 mg/kg i.p.). Three weeks after diabetes induction, rats were treated with minocycline (50 mg/kg, p.o.), aspirin (50 mg/kg, p.o.), or minocycline (50 mg/kg, p.o.) plus aspirin (50 mg/kg, p.o.) for a period of 3 weeks. At the end of week 6, I/R injury was induced by ligating the left anterior descending coronary artery for 30 min followed by 2 h reperfusion. RESULTS: Percentage infarct volume, arrhythmias, mortality, collagen level and MMP-2 and MMP-9 level were significantly increased in vehicle-treated diabetic group when compared with normoglycemic rats. Treatment with a combination of minocycline and aspirin decreased percentage infarct volume, arrhythmias, mortality and collagen level when compared with vehicle-treated diabetic controls and showed reduced levels of MMP-2 and MMP-9. CONCLUSIONS: Results of the present study suggest that the combination of minocycline and aspirin prevent worsening of AMI in diabetic rats.
BACKGROUND AND AIMS: Diabetes is a risk factor for exacerbated outcome after acute myocardial infarction (AMI) and doubles the risk of mortality after MI. Increased levels of MMP-2 and MMP-9 in diabetes cause vascular remodelling, which leads to cardiovascular complications of diabetes. We hypothesized that inhibition of MMP-2 and MMP-9 can reduce worsening of myocardial ischemia in diabeticpatients. Further, we hypothesized that minocycline induced MMP-2 and MMP-9 inhibition will be potentiated by aspirin and the combination of both drugs will prevent worsening of MI in diabeticpatients. In the present study, efficacy of combination of minocycline and aspirin to attenuate exacerbation of myocardial ischemia/reperfusion (I/R) injury in diabeticrats was evaluated. METHODS:Diabetes was induced in male Wistar rats by streptozotocin (55 mg/kg i.p.). Three weeks after diabetes induction, rats were treated with minocycline (50 mg/kg, p.o.), aspirin (50 mg/kg, p.o.), or minocycline (50 mg/kg, p.o.) plus aspirin (50 mg/kg, p.o.) for a period of 3 weeks. At the end of week 6, I/R injury was induced by ligating the left anterior descending coronary artery for 30 min followed by 2 h reperfusion. RESULTS: Percentage infarct volume, arrhythmias, mortality, collagen level and MMP-2 and MMP-9 level were significantly increased in vehicle-treated diabetic group when compared with normoglycemic rats. Treatment with a combination of minocycline and aspirin decreased percentage infarct volume, arrhythmias, mortality and collagen level when compared with vehicle-treated diabetic controls and showed reduced levels of MMP-2 and MMP-9. CONCLUSIONS: Results of the present study suggest that the combination of minocycline and aspirin prevent worsening of AMI in diabeticrats.
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