Protective effects of gallic acid against methotrexate-induced toxicity in rats

Acta Chir Belg. 2018 Jun;118(3):152-160. doi: 10.1080/00015458.2017.1394672. Epub 2017 Oct 25.

Abstract

Background: Methotrexate, as a chemotherapy drug, can cause chronic liver damage and oxidative stress. Aim of this study was to evaluate the preventive effect of gallic acid (GA) on methotrexate (MTX)-induced oxidative stress in rat liver.

Methods: Twenty-eight male rats were randomly divided into four groups as control, MTX (20 mg/kg, i.p.), MTX + GA (30 mg/kg/day, orally) and GA treated. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were used as biochemical markers of MTX-induced hepatic injury. Malondialdehyde (MDA) and glutathione (GSH) levels and hepatic antioxidant enzymes activities including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were assayed in liver tissue. The expression of SOD2 and GPx1 genes were evaluated by real-time RT-PCR and liver histopathology was evaluated by light microscopy.

Results: The result obtained from current study showed that GA remarkably reduced MTX-induced elevation of AST, ALT and ALP and increased MTX-induced reduction in GSH content, GPx, CAT and SOD activity as well as GPx1 and SOD2 gene expressions. Histological results showed that MTX led to liver damage and GA could improve histological changes.

Conclusions: Our results indicate that GA ameliorates biochemical and oxidative stress parameters in the liver of rats exposed to MTX.

Keywords: Methotrexate; gallic acid; oxidative stress; rat.

MeSH terms

  • Alanine Transaminase / blood
  • Analysis of Variance
  • Animals
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood
  • Biopsy, Needle
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / pathology*
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Disease Models, Animal
  • Gallic Acid / pharmacology*
  • Immunohistochemistry
  • Liver Function Tests
  • Male
  • Methotrexate / pharmacology
  • Methotrexate / toxicity*
  • Multivariate Analysis
  • Oxidative Stress / drug effects*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction / methods
  • Reference Values
  • Risk Assessment
  • Superoxide Dismutase / blood

Substances

  • Biomarkers
  • Gallic Acid
  • Superoxide Dismutase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Methotrexate