The impact of methotrexate on lung inflammatory and apoptotic pathway biomarkers-The role of gallic acid

Biomed Pharmacother. 2016 Dec:84:1689-1696. doi: 10.1016/j.biopha.2016.10.077. Epub 2016 Nov 18.

Abstract

Backgrounds: The aim of this study was to investigate the effects of methotrexate (MTX) on the lung via inflammatory and apoptotic pathway biomarkers and the role of gallic acid (GA).

Methods: In this study, twenty four male Wistar-Albino rats weighing 300-350g were divided into 3 groups as follows; Control group (0.1ml/oral saline, for 7 days+2nd day i.p.). MTX group (20mg/kg, single dose, on 2nd day). MTX+GA group (15mg/kg, orally, for 7 days). Comet analysis, oxidant-antioxidant status, IMA were conducted. Histopathological analyses were evaluated.

Results: Comet assay on the blood, TOS and OSI values in the lung were increased in the group II compared with the control group (p<0.05). GA significantly reduced the comet score and IMA levels in the blood, TOS and OSI values in the lung tissue in group III compared with group II (p<0.05). Immunohistochemically PGE2, TNF-α, CRP, serum SAA, Caspase 3 and Caspase 9 expressions significantly increased in group II compared with the control group (p<0.001) and GA treatment ameliorated these parameters significantly in group III compared with group II (p<0.001).

Conclusions: MTX caused oxidative stress and DNA damage in the blood tissue and caused oxidative damage, inflammation and apoptosis in the lung tissue.

Keywords: Gallic acid; Inflammation; Lung; Methotrexate; Oxidative stress.

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Biomarkers / metabolism*
  • C-Reactive Protein / metabolism
  • Caspases / metabolism
  • Comet Assay
  • Dinoprostone / metabolism
  • Gallic Acid / pharmacology
  • Gallic Acid / therapeutic use*
  • Immunohistochemistry
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Methotrexate / adverse effects*
  • Oxidative Stress / drug effects
  • Pneumonia / blood
  • Pneumonia / chemically induced*
  • Pneumonia / drug therapy*
  • Pneumonia / pathology
  • Rats, Wistar
  • Serum Amyloid A Protein / metabolism
  • Signal Transduction* / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Biomarkers
  • Serum Amyloid A Protein
  • Tumor Necrosis Factor-alpha
  • Gallic Acid
  • C-Reactive Protein
  • Caspases
  • Dinoprostone
  • Methotrexate