Effect of vitamin B12 on methotrexate-induced cardiotoxicity in rats

Kuloǧlu N., KARABULUT D., KAYMAK E., Akin A. T., Ceylan T., Yildirim A. B., ...More

IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, vol.27, no.6, pp.733-739, 2024 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 27 Issue: 6
  • Publication Date: 2024
  • Doi Number: 10.22038/ijbms.2024.74161.16120
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Index Islamicus, Veterinary Science Database, Directory of Open Access Journals
  • Page Numbers: pp.733-739
  • Keywords: Erythropoietin, Hypoxia-inducible factor-1 Methotrexate, Vascular endothelial growth - factor, Vitamin B12
  • Erciyes University Affiliated: Yes


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 B12 on this toxicity. Materials and Methods: A total of 32 rats were used in our study and 4 groups were formed. Control group, Vit B12 group (3 mu g/kg B12 for 15 days, IP), MTX group (20 mg/kg MTX single dose on day 8 of the experiment, IP), MTX +Vit B12 group (3 mu g/kg, IP ), Vit B12 throughout the 15 days, and a single dose of 20 mg/kg MTX (IP) on day 8 of the experiment. Immunohistochemically, expressions of hypoxia-inducible factor 1 alpha (HIF1-alpha), vascular endothelial growth factor receptor -2 (VEGFR-2), erythropoietin (EPO), and interleukin-6 (IL -6) 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 HIF1-alpha and VEGFR-2 increased significantly in the MTX group, while IL -6 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 B12 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 B12 before and after MTX administration to replace the folate that MTX has reduced.