Antioxidative Stress and Antiapoptosis Effect of Chitosan Nanoparticles to Protect Cardiac Cell Damage on Streptozotocin-Induced Diabetic Rat

Abstract

The antioxidant can inhibit oxidative stress and apoptosis, which has a role in an important mechanism on diabetic-induced cardiac cell damage. The research goal was to prove the antioxidative stress and antiapoptosis effect of chitosan nanoparticles as a cardioprotector in streptozotocin-induced diabetic rats. Scanning electron microscope (SEM) and dynamic light scattering (DLS) characterize the chitosan nanoparticles. This research is a laboratory experiment which consists of the control group (rats were given distilled water), the streptozotocin group (rats were injected streptozotocin at dose of 55 mg/kg BW i.p), and the chitosan nanoparticle group (rats were given streptozotocin at dose 55 mg/kg BW i.p, and then given chitosan nanoparticles at dose 75 mg/kg BW, 150 mg/kg BW, and 300 mg/kg BW peroral). Creatine kinase-myoglobin (CK-MB) and lactate dehydrogenase (LDH) were measured from the blood sample. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) from cardiac tissue were examined by ELISA; nuclear factor erythroid 2-related factor 2 (Nrf2) was evaluated by western blotting; B-cell lymphoma 2 (Bcl-2) and Caspase-3 expression were investigated by immunohistochemical staining and also were evaluated histological preparation by hematoxylin & eosin (H&E) staining. The chitosan nanoparticles have a rough surface and an irregular shape. Its size is $247.3\pm 38.1\mu \text{m}$ . Streptozotocin injection significantly increased the levels of CK-MB, LDH, MDA, and expression of caspase-3. In contrast, the levels of SOD, GPx, Nrf2, and expression of Bcl-2 decreased as compared with the control group ( $p<0.05$ ). This is accompanied by the loss of normal cardiac cell structure and necrosis. The administration of chitosan nanoparticles significantly reduced levels of CK-MB, LDH, MDA, and expression of Caspase-3. However, the levels of SOD, GPx, Nrf2, and expression of Bcl-2 increased as compared with the streptozotocin group ( $p<0.05$ ). And also, chitosan nanoparticles inhibited cell necrosis in diabetic rats. This study suggests that the administration of chitosan nanoparticles can protect cardiac cell damage in diabetic rats through antioxidative stress by decreasing ROS and increasing Nrf2 expression, level of SOD, and GPx and through antiapoptosis by increasing expression of Bcl-2 and decreasing expression of Caspase-3.