Cardioprotective effect of vitamin D3 on cisplatin-induced cardiotoxicity in male mice: role of oxidative stress

Cisplatin (CP) is a chemotherapy drug used in a broad spectrum of cancer. The current study investigated the protective effect of vitamin D3 (vit-D3) on CP-induced cardiotoxicity. Forty-two male Balb-c mice (20-25 g) were divided into seven groups (GP), 6 per/group were included: GP1 was considered the control group, GP2 received a single dose of I.V. injection of cisplatin (10 mg/kg). Seven days before cisplatin injection on GP3 and GP4 as pre-treatment, vit-D3 was injected I.P. with the doses of 500 IU/kg and 1000 IU/kg, respectively. GP5 and GP6 were considered the treatment groups, were injected cisplatin (10 mg/kg, I.V), and 15 days later, received vit-D3 (500 IU/kg and 1000 IU/kg, I.P) for 7 days. GP7 was the positive control group, which received vit-D3 at a dose of 500 IU/kg (I.P.) for 7 days. Tissues samples and blood serum were collected for biochemical and histopathological investigations. CP injection significantly increased (p < 0.001) LDH, Troponin I, CK-MB, malondialdehyde (MDA), and nitric oxide (NO) levels, but total antioxidant capacity (TAC) levels were significantly reduced. Histological findings showed cardiac muscle rupture, myocardial fiber necrosis, edema, and pyknotic nuclei, indicating cardiac damage. In both pre-treatment and treatment protocol, vit-D3 could improve the histological and biochemical parameters and prevented from the CP toxicity. Vit-D3 significantly could prevent the CP cardiotoxicity in pre-treatment groups, and partially improve the damage of chemotherapy in treatment group. However, further research is necessary to establish the potential of vit-D3 in preventing or ameliorating cisplatin-induced cardiotoxicity.