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    Effect of vitamin B12 on methotrexate-induced cardiotoxicity in rats
    (Mashhad Univ Med Sciences, 2024) Kuloglu, Nurhan; Karabulut, Derya; Kaymak, Emin; Akin, Ali Tugrul; Ceylan, Tayfun; Yildirim, Aysegul Burcin; Yakan, Birkan
    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.
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    Thymoquinone reduces methotrexate-induced heart damage: a histopathological study in rats
    (Cukurova Univ, Fac Medicine, 2023) Yildirim, Aysegul Burcin; Kaymak, Emin; Ceylan, Tayfun; Akin, Ali Tugrul; Kuloglu, Nurhan; Sayan, Meryem; Deger, Necla
    Purpose: The study aimed to evaluate the effect of thymoquinone on cardiac tissue in MTX-induced cardiac toxicity in rats with various parameters.Materials and Methods: Group I (n=8) was administered intraperitoneal saline for 10 days. Intraperitoneal olive oil was applied to Group II (n=8) for 10 days. Group III (n=8) received 10 mg/kg Thymoquinone (THQ) intraperitoneally for 10 days. Group IV (n=8) was administered a single dose of 20 mg/kg Methotrexate (MTX), 500 mg/20 ml, intraperitoneally on the 1st day of the experiment. Group V (n=8) MTX: 20 mg/kg single dose intraperitoneally on the 1st day; THQ: 10mg/kg i.p. administered for 10 days. Since Methotrexate was in liquid form, no solvent was used. At the end of the experimental period, the rats were sacrificed for analysis of heart tissue. The structure of heart tissue was evaluated by hematoxylin-eosin staining. Immunohistochemically, Connexin-43, HSP90, and HIF- 1 alpha antibodies were stained.Results: Group IV was found to have histopathological deterioration, which was ameliorated by THQ. In addition to this; Connexin-43 immunoreactivity was the lowest in Group IV compared to other groups: 108.5 +/- 7.4. Compared to other groups, HSP90 immunoreactivity was highest in Group IV: 103.6 +/- 10.4. Compared to other groups, HIF-1 alpha immunoreactivity was highest in Group IV: 95.2 +/- 9.1.Conclusion: Thymoquinone has a positive effect on Connexin-43, one of the proteins providing conduction in intercalary discs, HSP90, one of the chaperones in the cell and HIF-1 alpha expression against MTX toxicity. At the same time, THQ provides a significant improvement in cardiac tissue histopathologically by showing a cardioprotective effect.