Background: Isoproterenol (ISO) is a non-selective β-adrenergic agonist. Our aims were to investigate
the autophagy and cell death pathways including apoptosis and necrosis in ISO-induced cardiac injury in a dosedependent
Methods: Male Sprague-Dawley rats were treated for 24 hours with I. vehicle (saline); II. 0.005 mg/kg ISO; III.
0.05 mg/kg ISO; IV. 0.5 mg/kg ISO; V. 5 mg/kg ISO; VI. 50 mg/kg ISO, respectively. Hearts were isolated and
infarct size was measured. Serum levels of Troponin T (TrT), lactate dehydrogenase (LDH), creatine kinase isoenzyme
MB (CK-MB) were measured. TUNEL assay was carried out to monitor apoptotic cell death and Western
blot was performed to evaluate the level of autophagic and apoptotic markers.
Results: Survival rate of animals was dose-dependently decreased by ISO. Serum markers and infarct size revealed
the development of cardiac toxicity. Level of Caspase-3, and results of TUNEL assay, demonstrated that
the level of apoptosis was dose-dependently increased. They reached the highest level in ISO 5 and it decreased
slightly in ISO 50 group. Focusing on autophagic proteins, we found that level of Beclin-1 was increased in a
dose-dependent manner, but significantly increased in ISO 50 treated group. Level of LC3B-II and p62 showed
the same manner, but the elevated level of p62 indicated that autophagy was impaired in both ISO 5 and ISO 50
Conclusion: Taken together these results suggest that at smaller dose of ISO autophagy may cope with the toxic
effect of ISO; however, at higher dose apoptosis is initiated and at the highest dose substantial necrosis occurs.