The potential cardioprotective effect of alpha-lipoic acid on isoproterenol-induced myocardial infarction in rats

Dr. Al-Rasheed, Nawal1, Dr. Al-Rasheed, Nouf1, Dr. Abdel Baky, Nayira1, Dr. Zaghloul, Iman2, Prof. Radwan, Mahasen2. 1King saud University Department of Pharmacology, University Road, 86968 P.O. Box, Saudi Arabia; 2King Saud University Clinical Pharmacy, University Road, 86968 P.O. Box, Saudi Arabia.

This study was designed to examine the cardioprotective effect of alpha-lipoic acid against isoproterenol (ISO)-induced myocardial infarction in rats. Electrocardiograph parameters were monitored, levels of lactate dehydrogenase (LDH), creatine phosphokinase–MB (CPK-MB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the plasma, as well as cardiac antioxidative parameters were measured. Histopathological examination of heart tissues was also performed. Subcutaneous injection of ISO (85 mg kg-1at an interval of 24 h for 2 days) to male Wistar albino rats showed significant increase in the levels of diagnostic cardiac marker enzymes in the plasma, as well as a significant elevation in ST segment (0.141±0.012 vs. 0.056±0.002 mv in control, P<0.001). In addition, the levels of thiobarbituric acid reactive substances were significantly increased (104.7±4.7 vs. 51.03±4.1 nmol g-1 tissue in control, P<0.001) , while the activities of superoxide dismutase SOD (3.06±0.33 vs. 8.86±0.72 µmol g-1 tissue in control , P<0.001) and catalase CAT (14.22±1.05 vs. 43.14±2.68 U mg-1 protein in control, P<0.001) as well as the levels of reduced glutathione (0.61±0.02 vs. 1.76±0.07 U mg-1protein in control, P<0.001) in the heart tissue were significantly decreased. Pretreatment with either alpha-lipoic acid (100 mg kg-1, p.o.) or amlodipine (5.0 mg kg-1, p.o.) daily for a period of 15 and 5 days, respectively significantly altered almost all the changes in the parameters of isoproterenol-induced myocardial injury that mentioned above. The combination of alpha-lipoic acid and amlodipine significantly reduced the elevation in the levels of diagnostic marker enzymes in plasma of experimental animals and almost restored normal ECG-patterns. In addition, this combination exerted a synergistic antioxidant effect by blocking the induction of lipid peroxidation (59.2±3.4 nmol g-1 tissue), and exerted a tendency to prevent the ISO-induced alterations in the level of reduced glutathione (1.47±0.06 mol g-1 tissue), as well as in the activities of antiperoxidative enzymes (SOD [8.05± 0.57 U mg-1 protein], and CAT [34.49± 1.5 U mg-1 protein]). Histopathological observations were also in correlation with the biochemical parameters. These findings indicate a synergistic cardioprotective effect of alpha-lipoic acid and amlodipine on acute myocardial infarction induced by ISO in rats.