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1 Department of Pharmacology, National University of Singapore, Singapore, Singapore; Deartment of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China
2 Emergency Department, National University Hospital, Singapore, Singapore
3 Department of Pharmacology, National University of Singapore, Singapore, Singapore
4 Department of Biochemistry, National University of Singapore, Singapore, Singapore
* To whom correspondence should be addressed. E-mail: phczhuyz{at}nus.edu.sg.
In our current study, we aimed to determine whether nitroparacetamol (NO donor) and paracetamol exhibit cardioprotective effects. Myocardial infarction (MI) was induced in Wistar rats and drug treatment was started 1 week before surgery. Mortality rate at 2 days after MI induction was compared. Male Wistar rats weighing between 220-250 g were used. Treatment groups included vehicle (saline), paracetamol and nitroparacetamol (NO-paracetamol). These drugs were given via the intraperitoneal route at doses of 5mg/kg/day, 5mg/kg/day and 15 mg/kg/day, respectively. Mortality rate for vehicle (n=80), paracetamol (n=79) and NO-paracetamol (n=76), groups were 37.5%, 21.5% and 26.3%, respectively. A corresponding reduction in infarction size in the groups with better survival rate was noted. Thus, infarction size for the vehicle group was 44.8% (±6.1%) of the left ventricle (LV). For the paracetamol and NO-paracetamol groups, infarction size was 31.3% (±5.6%) and 30.7% (± 8.1%) of the LV, respectively. NO-paracetamol and paracetamol administration in this way did not have any discernible effects on blood pressure or post-myocardial infarction temperature in these animals. Both paracetamol and NO-paracetamol treated groups showed increased activities of Catalase (CAT) and superoxide dismutase (SOD) compared to the vehicle group. They could attenuate eNOS, iNOS, nNOS, COX-1 and COX-2 genes expression after MI. The observation that both nitroparacetamol and paracetamol produce a lower mortality rate than vehicle indicates the potential clinical significance of the cardioprotective effects of these drugs.
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