Abstract
Advanced glycation end products (AGEs) have been reported to serve an important role in the stiffening of cardiac tissues and myocardial cell injury. Serious myocardial cell injury can result in various heart diseases with high mortality. Halofuginone (HF), which possesses marked anti‑inflammatory and antifibrotic effects, has recently been applied to inhibit the effects of cardiac stress. The present study aimed to investigate the potential effects of HF and its underlying mechanism in the treatment of AGEs‑induced H9C2 cardiomyocyte damage. The western blot results of the present study demonstrated that HF may reduce the expression levels of myocardial injury markers, including myoglobin, creatine kinase MB and cardiac troponin I. In addition, flow cytometric analysis indicated that the production of reactive oxygen species (ROS) was significantly decreased by HF. Additionally, endoplasmic reticulum (ER) stress was suppressed in response to treatment with HF, as observed by low expression levels of ER stress‑associated proapoptotic proteins (CCAAT/enhancer‑binding protein homologous protein and cleaved caspase‑12); overexpression of prosurvival proteins (growth arrest and DNA damage‑inducible protein GADD34 and binding immunoglobulin protein) was also reported. Furthermore, the expression levels of microtubule‑associated proteins 1A/1B light chain 3B (LC3)II/LC3I and Beclin 1 were elevated, whereas P62 expression levels were reduced following treatment with HF. These findings, together with immunofluorescence staining of LC3, indicated that HF may induce autophagy. Finally, the protective effects of HF on AGEs‑treated H9C2 cells were reversed following treatment with the inhibitor 3‑methyladenine, as indicated by inhibition of autophagy, and increases in apoptosis, ROS production and the ER stress response. Collectively, the findings of the present study suggested that the protective effects of HF against AGEs‑induced myocardial cell injury may be associated with the induction of autophagy and amelioration of ROS‑mediated ER stress and apoptosis. These findings may contribute to the development of a novel therapeutic method to inhibit the progression of myocardial cell injury.