Effect of mebudipine on oxidative stress and lipid peroxidation in myocardial ischemic-reperfusion injury in male rat

Abstract

• Background: Myocardial infarction (MI) is the acute condition of necrosis in myocardium which occurs as a result of imbalance between coronary blood supply and myocardial demand. The resultant oxidative stress excess leads to worsen the condition. The aim of this study was to investigate the effect of mebudipine, a new dihydropyridine calcium channel blocker, on lipid peroxidation and antioxidant enzymes in myocardial ischemia-reperfusion injury.
• Materials and Methods: Male Wistar rats (250-300g) were randomly divided to Control-ischemic, mebudipine-ischemic and vehicle (ethanol-ischemic) groups. The hearts of anaesthetized rats were removed and mounted on Langendorff apparatus and perfused by Krebs-Henseleit solution under constant pressure of 75mmHg at 37°C. Ischemic groups were received 30 min global ischemia and 120min reperfusion and the mebudipine and vehicle groups received mebudipine (0.1nM) or ethanol (0.01%)-enriched solution 25min before global ischemia. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase levels of heart tissue samples were determined by commercial specific Kits.
• Results: Mebudipine significantly reduced the MDA level (2.3±0.07 nmol/mg protein) as the biochemical indicator of oxidative damage and lipid peroxidation product as compared with those of vehicle (4.6± 0.01 nmol/mg protein) and control groups (4.8 ± 0.09 nmol/mg protein). Furthermore, antioxidant enzymes SOD (0.1±0.006 in drug vs. 0.037±0.009 U/mg Protein in control), GPX (16±0.009 in drug vs. 0.068±0.01 U/mg Protein in control) and catalase activities (0.075±0.006 in drug vs. 0.028±0.002 U/mg Protein in control), activities of myocardium were significantly increased by mebudipine (P<0.01).
• Conclusion: Our results showed that mebudipine may have antioxidant activity against myocardial ischemia-reperfusion injury, since it decreased oxidative stress by enhancing the enzymatic antioxidant defense and inhibiting the lipid peroxidation. Thus, this drug can reduce the intensity of cardiac ischemic insults.
• Keywords: Ischemia, lipid peroxidation, mebudipine, myocardial, oxidative stress, reperfusion