Abstract
In the study, we aimed to show the effects of vitamin B12 on the necrosis caused by methotrexate (MTX), a folic acid antagonist. Thirty-two rats were randomly assigned to four groups of eight rats per group. Control (n = 8), Vit B12 (n = 8) 3 μg/kg/ip B12 (15 days) per day throughout the experiment, MTX (n = 8) injected with a single dose of 20 mg/kg/ip MTX on 8th day of experiment, MTX + Vit B12 (n = 8) injected with a single dose of 20 mg/kg ip methotrexate on 8th day of experiment + 3 μg/kg/ip Vit B12 (15 days) per day throughout the experiment. Oxidant (TOS)/antioxidant (TAS) system, TNF-α and TGF-β levels, AST and ALT, serum vitamin B12 levels were determined in the tissue. Cyclooxygenase-2 (Cox-2), receptor-interacting protein kinase 1 (RIP1) and 3 (RIP3) immunohistochemistry were applied to the liver tissue. TOS increased; TAS decreased; TNF-α and TGF-β levels increased; AST and ALT levels changed after MTX hepatotoxicity. Vit B12 decreased significantly. COX-2, RIP1, and RIP3 immunoreactivity increased. Vit B12 showed improvement in all of the negative results. Vit B12 is an important supplement to be used against necrosis in tissue after MTX hepatotoxicity.
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This work was supported by Erciyes University the Scientific Research Projects Unit, TSA-2019-8673 project code.
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DK and EO designed and performed experiment. DK, ATA, EK, and BY contributed to analyzed the data. EO and NK performed the histological analyses. DK wrote the manuscript. The authors declare that all data were generated in-house and that no paper will was used.
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Ethical approval for the study was obtained from Erciyes University Animal Research Local Ethics Committee and the ethics at regulations were followed in accordance with national and institutional guidelines (date 2018, decision no. 18/116).
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Karabulut, D., Ozturk, E., Kuloglu, N. et al. Effects of vitamin B12 on methotrexate hepatotoxicity: evaluation of receptor-interacting protein (RIP) kinase. Naunyn-Schmiedeberg's Arch Pharmacol 393, 2473–2480 (2020). https://doi.org/10.1007/s00210-020-01992-1
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DOI: https://doi.org/10.1007/s00210-020-01992-1