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

Naunyn Schmiedebergs Arch Pharmacol. 2020 Dec;393(12):2473-2480. doi: 10.1007/s00210-020-01992-1. Epub 2020 Oct 14.

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: Methotrexate; Receptor-interacting protein kinase; Vitamin B12.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / toxicity*
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / enzymology*
  • Male
  • Methotrexate / toxicity*
  • Rats
  • Rats, Wistar
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*
  • Treatment Outcome
  • Vitamin B 12 / therapeutic use*

Substances

  • Antimetabolites, Antineoplastic
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Vitamin B 12
  • Methotrexate