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

Derya Karabulut1, Emel Ozturk2, Nurhan Kuloglu3,4

  • 1Histology-Embriology Department, Faculty of Medicine, Erciyes University, Köşk, Talas Avenue, 38030 Melikgazi-, Kayseri, Turkey. deryakkus@hotmail.com.

Naunyn-Schmiedeberg'S Archives of Pharmacology
|October 14, 2020
PubMed

Insights

Vitamin B12 supplementation can mitigate liver damage and necrosis caused by methotrexate (MTX) treatment. This study demonstrates that vitamin B12 improves biochemical markers and reduces inflammatory responses associated with MTX hepatotoxicity.

Area of Science:

  • Biochemistry
  • Toxicology
  • Pharmacology

Background:

  • Methotrexate (MTX) is a folic acid antagonist used in chemotherapy, known to cause hepatotoxicity.
  • MTX-induced liver injury is characterized by oxidative stress, inflammation, and cellular necrosis.
  • Understanding protective mechanisms against MTX hepatotoxicity is crucial for patient management.

Purpose of the Study:

  • To investigate the protective effects of vitamin B12 against methotrexate-induced liver necrosis in a rat model.
  • To evaluate the impact of vitamin B12 on oxidative stress markers, inflammatory cytokines, liver enzymes, and specific protein expressions in MTX-treated rats.

Main Methods:

  • Thirty-two rats were divided into four groups: Control, Vitamin B12, MTX, and MTX + Vitamin B12.
  • Hepatotoxicity was induced by a single dose of MTX (20 mg/kg).
  • Vitamin B12 (3 μg/kg/day) was administered throughout the experiment.
  • Assessed serum levels of vitamin B12, AST, ALT, TOS, TAS, TNF-α, and TGF-β.
  • Performed immunohistochemistry for COX-2, RIP1, and RIP3 in liver tissue.

Main Results:

  • MTX administration led to increased oxidative stress (TOS), decreased antioxidant capacity (TAS), elevated TNF-α and TGF-β, and altered AST/ALT levels.
  • MTX treatment significantly increased COX-2, RIP1, and RIP3 immunoreactivity in liver tissue.
  • Vitamin B12 supplementation notably improved all measured negative outcomes, including biochemical markers and inflammatory responses.
  • Serum vitamin B12 levels were significantly decreased in the MTX group and improved with B12 co-administration.

Conclusions:

  • Vitamin B12 demonstrates significant protective effects against MTX-induced liver necrosis and hepatotoxicity.
  • Vitamin B12 supplementation can counteract MTX-induced oxidative stress, inflammation, and cellular damage markers.
  • Vitamin B12 is a valuable supplement for mitigating the adverse effects of methotrexate on liver tissue.
Keywords:
MethotrexateReceptor-interacting protein kinaseVitamin B12

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