Polydatin combats methotrexate-induced pulmonary fibrosis in rats: Involvement of biochemical and histopathological assessment

J Biochem Mol Toxicol. 2022 May;36(5):e23019. doi: 10.1002/jbt.23019. Epub 2022 Feb 17.

Abstract

Polydatin (PD) is a polyphenolic compound found naturally in many fruits such as grapes. It has anti-oxidant and anti-inflammatory activities that are of paramount importance for its pharmacological actions. This study aimed to explore possible protective effects of PD against methotrexate (MTX)-induced pulmonary fibrosis in rats. A single oral dose of MTX (14 mg/kg) per week for 2 weeks caused a significant decrease in glutathione (GSH) content with a marked increase in transforming growth factor-beta (TGF-β), alpha-smooth muscle actin (α-SMA), pulmonary content of malondialdehyde (MDA), interleukin-1β (IL-1β), Hydroxyproline, tumor necrosis factor-alpha (TNF-α), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as compared with the control group. Contrarily, daily administration of PD (25, 50, and 100 mg/kg, p.o.) for 14 days concomitantly with MTX ameliorated MTX-induced pulmonary fibrosis as indicated by mitigation of the previously mentioned biochemical parameters and histopathological changes in a dose-dependent manner. In conclusion, the protective effect of PD against pulmonary fibrosis induced by MTX in rats might be attributed to its anti-oxidant, anti-inflammatory as well as anti-fibrotic effects.

Keywords: dexamethasone; methotrexate; oxidative stress; polydatin; pulmonary fibrosis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Glucosides* / pharmacology
  • Glutathione / metabolism
  • Methotrexate* / toxicity
  • Oxidative Stress
  • Pulmonary Fibrosis* / chemically induced
  • Pulmonary Fibrosis* / drug therapy
  • Rats
  • Stilbenes* / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Glucosides
  • Stilbenes
  • Glutathione
  • polydatin
  • Methotrexate