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 |
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Main Authors: | , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
Berlin/Heidelberg
Springer Berlin Heidelberg
01-12-2020
Springer Nature B.V |
Subjects: | |
Online Access: | Get full text |
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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. |
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ISSN: | 0028-1298 1432-1912 |
DOI: | 10.1007/s00210-020-01992-1 |