Preventive Effect of Amiodarone During Acute Period in Isoproterenol-Induced Myocardial Injury in Wistar Rats

Abstract

The ability of amiodarone to prevent pathological changes and oxidative stress after isoproterenol (ISO)-induced myocardial injury was investigated in rats. A better understanding of the processes involved in the pathophysiology of myocardial infarction has led to the search for drugs that can limit the extent of myocardial injury. Amiodarone was administered to groups of rats once per day for 30 days. On days 29 and 30, the rats of the ISO control and drug treatment groups were administered 180 mg/kg ISO subcutaneously at an interval of 24 h for two consecutive days. In the control groups, clinical indicators, such as creatine kinase-isoenzymes and troponin-I, were found to be statistically higher than in the drug groups. Parallel to this increase in indicators, a significant decrease in glutathione levels and activities of superoxide dismutase and an increase in malondialdehyde level were detected. Biochemical and histopathologic results in the ISO-induced model of myocardial injury emphasize the beneficial action of amiodarone as a cardioprotective agent.

Valsartan, an Angiotensin II Receptor Blocker, Attenuates Cardiac Dysfunction and Oxidative Stress in Isoproterenol-Induced Cardiotoxicity

“…In the present study, ISO administration caused oxidative stress in heart as evidenced by the reduction in activities of myocardial SOD, catalase, and GSH levels [19][20][21]. Interestingly, valsartan treatment significantly increased these anti-oxidant enzymes levels.…”

“…ISO-induced MI is a well-authenticated model for screening of various drugs for their cardioprotective potential and also provides insight into the concerned mechanisms [3,6]. Furthermore, myocardial lesions produced by ISO in rats closely resembles to that of pathological state of human MI [6,19,25]. ISO through spontaneous auto-oxidation leads to the formation of adrenochrome which is implicated in the generation of highly toxic oxygen-derived free radicals.…”

“…Lipid peroxidation plays an important role in the pathogenesis of MI. A significant increase in the levels of lipid peroxidation product such as MDA in the heart indicates increased oxidative stress in ISO-induced rats [3,6,19,20]. Reactive oxygen species which are highly toxic by-products of aerobic metabolism are known to react extensively with cellular membranes and macromolecules thus enhancing formation of lipid peroxides and culminates into tissue damage.…”

Sesamol Attenuates Isoproterenol-induced Acute Myocardial Infarction via Inhibition of Matrix Metalloproteinase-2 and -9 Expression in Rats

“…MMP-2 [15][16][17][18] and MMP-9 [15] are upregulated in myocardial tissue in isoproterenol-induced MI. This leads to changes in the functional parameters of the heart: decreased SP and DP, increased HR [3,6,19], increased P, T, QRS, and PR wave durations in ECG [20,21], and the leakage of the myocardial injury markers CKMB and LDH in serum [3,[22][23][24]. Histopathologic analysis of the isoproterenol-treated myocardial tissue revealed an infarcted zone with inflammation, myofibrillar degeneration, and necrosis, which agrees with the findings in other studies [3,22,25].…”

“…This leads to changes in the functional parameters of the heart: decreased SP and DP, increased HR [3,6,19], increased P, T, QRS, and PR wave durations in ECG [20,21], and the leakage of the myocardial injury markers CKMB and LDH in serum [3,[22][23][24]. Histopathologic analysis of the isoproterenol-treated myocardial tissue revealed an infarcted zone with inflammation, myofibrillar degeneration, and necrosis, which agrees with the findings in other studies [3,22,25]. MMPs, a large family of endopeptidases, degrade extracellular matrix proteins, and are fundamental for tissue remodeling, including heart tissue [26][27][28].…”