Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Vitamin D: An effective therapy against methotrexate-induced cardiotoxicity

Tuba Ozcan Metin , Alper Yalcin

Department of Histology and Embryology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey;

For correspondence:- Tuba Metin Email: tubaozcanmetin@gmail.com Tel:+903443002667

Accepted: 27 August 2023 Published: 30 September 2023

Citation: Metin TO, Yalcin A. Vitamin D: An effective therapy against methotrexate-induced cardiotoxicity. Trop J Pharm Res 2023; 22(9):1841-1847 doi: 10.4314/tjpr.v22i9.10

© 2023 The authors.
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Abstract

Purpose: To determine the potential cardioprotective effect of vitamin D (VD) against methotrexate (MTX) induced cardiotoxicity.

Methods: A total of thirty-five (35) rats were randomly assigned to five equal groups. Control group received no treatment; MTX group received intraperitoneal (IP) injection of MTX in a single dose of 20 mg/kg on day 8; VD group received 200 IU/kg VD daily dissolved in sunflower oil orally; sunflower oil (SO) group received 1 mL/kg/day SO orally; MTX + VD group received a single dose of MTX (20 mg/kg, IP) on day 8 and VD (200 IU/kg, orally) for 21 days. Myocardial tissue samples were harvested and used for clinical chemistry, histopathological, and ultrastructural evaluation.

Results: Histopathological damage in MTX group was more severe than in control group under both light and electron microscopy. expression of transient receptor potential melastatin 2 (TRPM2) and caspase-3 markers was significantly higher in MTX group (p < 0.05). Glutathione peroxidase (GSH-Px) enzyme activity in cardiac tissue was lower in MTX group, whereas malondialdehyde (MDA) levels increased significantly (p < 0.05). In MTX + VD group, VD treatment alleviated histopathological damage and significantly lowered TRPM2 and caspase-3 expressions (p < 0.05). Vitamin D also reduced tissue MDA levels, and increased GSH-Px activity albeit non-significantly (p > 0.05),

Conclusion: These findings suggest that VD exerts an ameliorative effect on MTX-induced cardiotoxicity in rats. Therefore, TRPM2 channel affords a novel therapeutic approach for treatment of diseases related to chemotherapy-induced oxidative stress.

Keywords: Cardiotoxicity, Caspase-3, Methotrexate, TRPM2, Vitamin D