Hydroxyurea protects against diabetic cardiomyopathy by inhibiting inflammation and apoptosis

Hydroxyurea (HU), a small molecule with various biological properties, was used in myeloproliferative, tumorous, and non-hematological diseases. However, whether HU plays a role in diabetic cardiomyopathy (DCM) remains unclear. Our study aimed to investigated whether HU could ameliorate DCM or not. Induction of type 1 diabetes mellitus (T1DM) in C57BL/6 J mice was achieved by intraperitoneal injection of streptozotocin (STZ). Mice in control and diabetic groups were treated with HU (20 mg/kg) in drinking water for 16 weeks. Our data showed that diabetic mice had significantly increased FBG level and decreased body weight, along with abnormal diastolic function and myocardial fibrosis. Inflammatory factors including TNF-α, IL-1β, IL-6, ICAM, VCAM, and apoptosis-related proteins including caspase-3 and BAX were significantly up-regulated in heart tissues. HU treatment remarkably improved these changes. Similarly, application of HU (5 µM) significantly improves the survival rate of high glucose (HG)-treated H9C2 cells. Thus, HU rescued the cardiomyocytes via inhibition of apoptosis and inflammation in DCM.