Mechanism of streptozotocin to induce cardiac fibrosis through TNFa and Bcl2 pathways in in silico and in vivo study

Background: Cardiac fibrosis is often associated with various heart-related problems such as heart failure, atrial arrhythmia, and sudden cardiac death, making it a leading cause of death globally. Diabetes-associated fibrosis, on the other hand, is influenced by activated cardiac fibroblasts and potentially involves fibrosis-inducing activity of macrophages, cardiomyocytes, and vascular cells. Streptozotocin (STZ) is a known diabetogenic agent, but inadequate preclinical data in animal models hinders its clinical success. Aim: This study aims to provide practical guidelines for STZ utilization in inducing diabetes-associated cardiac fibrosis. Methods: The research was conducted in vivo using white rats (Rattus norvegicus) of the Wistar strain, induced with STZ at doses of 30 mg/KgBW and 50 mg/KgBW per injection. Observations were carried out in the 4th and 8th weeks, consisting of the measurement of blood sugar levels and the examination of heart muscle cell fibrosis. Subsequently, in silico validation of STZ’s affinity with inflammatory receptors causing diabetes pathology, such as TNFα and Bcl2, was performed. Results: The study results indicated that the administration of STZ led to an increase in random blood sugar levels and extensive fibrosis of heart muscle cells in mice. The optimal dose for the diabetes model experimented in this study was 50 mg/KgBW for 8 weeks. In silico tests revealed an affinity for TNFα (PDB ID 2AZ5) and Bcl2 (PDB ID 6QGH). Conclusion: Consequently, it can be concluded that administering STZ to mice at a dose of 50 mg/KgBW for 8 weeks is an effective inducer of a diabetes-associated cardiac fibrosis model.