Melatonin protects against methotrexate hepatotoxicity in young rats: Impact of PI3K/Akt/mTOR signaling

J Biochem Mol Toxicol. 2023 May;37(5):e23323. doi: 10.1002/jbt.23323. Epub 2023 Mar 8.

Abstract

With the improvement in children's acute lymphoblastic leukemia (ALL) care, the survival rate in children ALL has improved much. Methotrexate (MTX) plays an essential role in the success of children's ALL treatment. Since hepatotoxicity is commonly reported in individuals treated with intravenous or oral MTX, our study further examined the hepatic effect following intrathecal MTX treatment, which is an essential treatment for leukemia patients. Specifically, we examined the pathogenesis of MTX hepatotoxicity in young rats and explored the impact of melatonin treatment in protection against MTX hepatotoxicity. Successfully, we found that melatonin was able to protect against MTX hepatotoxicity.

Keywords: PI3K/Akt/mTOR; hepatotoxicity; melatonin; methotrexate.

MeSH terms

  • Animals
  • Chemical and Drug Induced Liver Injury* / etiology
  • Chemical and Drug Induced Liver Injury* / prevention & control
  • Melatonin* / pharmacology
  • Melatonin* / therapeutic use
  • Methotrexate / toxicity
  • Phosphatidylinositol 3-Kinases
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma*
  • Proto-Oncogene Proteins c-akt
  • Rats
  • TOR Serine-Threonine Kinases

Substances

  • Methotrexate
  • Melatonin
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • TOR Serine-Threonine Kinases
  • mTOR protein, rat