Cardioprotective effects of insulin-like growth factor (IGF-1) ina rat model of myocarditis

Doxorubicin (Dox) causes myocarditis due to its cardiotoxic effect due to oxidative damage. Insulin-like growth factor (IGF)-1 is a pharmacological agent with antiinflammatory, anti-apoptotic, and antioxidant properties, effective on the cardiovascular system. This study, it was aimed to elucidate the molecular mechanisms of IGF-1 and to investigate its cardioprotective effects in the Dox-induced myocarditis model. Wistar albino male rats Control, Dox (4mg/kg/week), IGF-1 (1 µg/kg two days apart) and Dox + IGF-1 (4mg/kg/week Dox and 1 µg/kg two days apart IGF- 1) and all applications were done intraperitoneally. At the end of the 4-week experimental protocol, sacrification was performed under Ketamine and Xylazine anesthesia. CK-MB and Troponin-I levels in blood serum were measured by biochemical analysis. Histopathological and immunohistochemical (Caspase-3 and ICAM-1) evaluations were performed on heart tissue. In addition, TNF-α, IL-6, TAS, and TOS levels were analyzed by ELISA method, and Beclin-1, SQSTM1, LC3, HIF-1α, iNOS, SERCA2a, and MasR gene expressions were analyzed by RT-PCR method in heart tissue. Dox administration increased histopathological and immunochemical scores, CK-MB, Troponin-I, TNF-α, IL-6 levels, and TOS/TAS ratio. As a result of molecular analyzes, caused cardiac damage by inducing the expressions of Beclin-1, SQSTM1, LC3, SERCA2a, MasR, and HIF-1α. There was a significant improvement in damage parameters after IGF-1 treatment. In a model of Dox-induced myocarditis, IGF-1 was found to exert a cardioprotective effect by inhibiting autophagy mediated by the SERCA2a/MasR signaling pathway. It was found that IGF-1 provides a therapeutic effect by regulating inflammatory processes, reducing oxidative damage, and inhibiting apoptotic cell death and autophagy in a model of Doxinduced myocarditis.