Effects of vitamin B12 on methotrexate hepatotoxicity: evaluation of receptor-interacting protein (RIP) kinase
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ORIGINAL ARTICLE
Effects of vitamin B12 on methotrexate hepatotoxicity: evaluation of receptor-interacting protein (RIP) kinase Derya Karabulut 1
&
Emel Ozturk 2 & Nurhan Kuloglu 1,3 & Ali Tuğrul Akin 4 & Emin Kaymak 5 & Birkan Yakan 1
Received: 17 June 2020 / Accepted: 7 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Receptor-interacting protein kinase . Methotrexate . Vitamin B12
Introduction Methotrexate (MTX) is an anti-cancer and anti-inflammatory drug used in the treatment of malignant diseases. It achieves this effect by inhibiting dihydrofolate reductase, which is essential for the generation of folate cofactors required for Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00210-020-01992-1) contains supplementary material, which is available to authorized users. * Derya Karabulut [email protected]; [email protected]; [email protected] 1
Histology-Embriology Department, Faculty of Medicine, Erciyes University, Köşk, Talas Avenue, 38030 Melikgazi-, Kayseri, Turkey
2
Histology-Embriology Department, Faculty of Medicine, Harran University, Sanlıurfa, Turkey
3
Health Care Services Elderly Care Department, Niğde Ömer Halisdemir University, Niğde, Turkey
4
Biology Department, Faculty of Science, Erciyes University, Kayseri, Turkey
5
Histology-Embriology Department, Faculty of Medicine, Bozok University, Yozgat, Turkey
purines and pyrimidine synthesis (Al Maruf et al. 2018; Chan and Cronstein 2010). MTX is used as oral, intramuscular, intravenous and subcutaneous dose-dependent. After absorption, almost 10% of the liver is partially inactive, 7hydroxymethotrexate (7-OH-MTX) is metabolized (Puig 2014). Taking high doses of MTX causes various side effects such as nausea, vomiting and abnormal liver functions, headache, fatigue a
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