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

KARABULUT D., Ozturk E., Kuloglu N., AKİN A. T., KAYMAK E., YAKAN B.

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, vol.393, no.12, pp.2473-2480, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 393 Issue: 12
  • Publication Date: 2020
  • Doi Number: 10.1007/s00210-020-01992-1
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.2473-2480
  • Keywords: Receptor-interacting protein kinase, Methotrexate, Vitamin B12, INDUCED OXIDATIVE STRESS, INDUCED LIVER-INJURY, NECROPTOSIS, ACID
  • Yozgat Bozok University Affiliated: Yes


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 mu g/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 mu g/kg/ip Vit B12 (15 days) per day throughout the experiment. Oxidant (TOS)/antioxidant (TAS) system, TNF-alpha and TGF-beta 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-alpha and TGF-beta 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.