Effects of vitamin B12 on methotrexate hepatotoxicity: evaluation of receptor-interacting protein (RIP) kinase

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 experimen...

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Published in:Naunyn-Schmiedeberg's archives of pharmacology Vol. 393; no. 12; pp. 2473 - 2480
Main Authors: Karabulut, Derya, Ozturk, Emel, Kuloglu, Nurhan, Akin, Ali Tuğrul, Kaymak, Emin, Yakan, Birkan
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-12-2020
Springer Nature B.V
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Summary: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.
ISSN:0028-1298
1432-1912
DOI:10.1007/s00210-020-01992-1