Effect of vitamin B۱۲ on methotrexate-induced cardiotoxicity in rats

Objective(s): Methotrexate (MTX) is a drug with anti-inflammatory and immunosuppressive effects and is also a folic acid antagonist. Our aim in this study is to determine the molecular mechanisms of cardiotoxicity caused by MTX, a chemotherapeutic drug, and to evaluate the protective effects of vitamin B۱۲ on this toxicity. Materials and Methods: A total of ۳۲ rats were used in our study and ۴ groups were formed. Control group, Vit B۱۲ group (۳ μg/kg B۱۲ for ۱۵ days, IP), MTX group (۲۰ mg/kg MTX single dose on day ۸ of the experiment, IP), MTX +Vit B۱۲ group (۳ μg/kg, IP ), Vit B۱۲ throughout the ۱۵ days, and a single dose of ۲۰ mg/kg MTX (IP) on day ۸ of the experiment. Immunohistochemically, expressions of hypoxia-inducible factor ۱α (HIF۱-α), vascular endothelial growth factor receptor-۲ (VEGFR-۲), erythropoietin (EPO), and interleukin-۶ (IL-۶) were evaluated in the heart tissue. Total catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured in the heart tissue. At the same time, ANP and NT-proBNP levels were measured in the blood serum.Results: In the study, the expression of HIF۱-α and VEGFR-۲ increased significantly in the MTX group, while IL-۶ and EPO significantly decreased. At the same time, CAT and SOD levels were significantly decreased and MDA levels increased significantly in the MTX group. While vitamin B۱۲ significantly corrected all these values, it also greatly reduced the increases in ANP and NT-proBNP levels caused by MTX.Conclusion: It is important to use Vit B۱۲ before and after MTX administration to replace the folate that MTX has reduced.

Keywords:

Erythropoietin , Hypoxia-inducible factor-۱ , Methotrexate , Vascular Endothelial Growth Factor , Vitamin B۱۲