Cardioprotective Effects of Dorzagliatin Against Streptozotocin-induced Diabetic Cardiomyopathy: Involvement of Anti-hyperlipidemic, Antioxidant, and Anti-inflammatory Mechanisms
Abstract
Diabetic cardiomyopathy (DCM) represents a critical clinical problem, manifesting as progressive functional and structural myocardial impairment independent of traditional cardiovascular comorbidities such as hypertension or coronary artery disease. Current treatment options largely rely on conventional heart failure protocols rather than disease-specific interventions. Consequently, the exploration of novel therapeutic strategies is essential to treat cardiomyopathy without inducing side effects. The present work aims to investigate the potential of dorzagliatin in an experimental rat model of DCM. To induce DCM, rats were intraperitoneally administered streptozotocin. Following the induction of diabetes, the animals were treated with dorzagliatin for a period of 6 weeks. Upon completion of the experimental protocol, physiological and metabolic markers, including body weight, fasting blood glucose (FBG) levels, insulin, and glycated hemoglobin (HbA 1C ), were evaluated. Additionally, the levels of lipid profile markers in the serum were evaluated using kits. The inflammatory cytokines and oxidative stress biomarker levels were evaluated in the heart tissue homogenates using kits. The cardiac tissues underwent histopathological analysis. Our findings suggest that dorzagliatin treatment led to an elevation in body weight and insulin levels, accompanied by a decrease in FBG and HbA 1C levels in rats with DCM. Dorzagliatin treatment considerably decreased the serum activities of cardiac injury marker enzymes in the streptozotocin (STZ)-induced rats. Additionally, dorzagliatin administration markedly elevated antioxidant defenses and suppressed proinflammatory cytokines in the STZ-induced rats. These beneficial effects were further corroborated by histological analysis, which showed preserved cardiac architecture. Our data demonstrate that dorzagliatin effectively ameliorates DCM in an STZ-induced rat model. In conclusion, our findings highlight that dorzagliatin holds potential as a therapeutic candidate for DCM.