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Febuxostat ameliorates methotrexate-induced lung damage.

S M Zaki1,2, G H A Hussein3, H M A Khalil4

  • 1Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia. zakysherif1@gmail.com.

Folia Morphologica
|July 10, 2020
PubMed
Summary
This summary is machine-generated.

Methotrexate overdose causes lung inflammation and fibrosis via oxidative stress and apoptosis. Febuxostat treatment protected the lungs by reducing inflammation and oxidative damage, preserving lung structure.

Keywords:
febuxostatlungmethotrexate

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Area of Science:

  • Pulmonary toxicology
  • Pharmacology
  • Inflammation research

Background:

  • Methotrexate (MTX) overdose can cause significant lung damage.
  • Understanding the mechanisms of MTX-induced lung injury is crucial.
  • Investigating potential protective agents like febuxostat is warranted.

Purpose of the Study:

  • To assess lung structural damage from MTX overdose.
  • To investigate the mechanisms of MTX-induced lung injury, including oxidative stress, apoptosis, and inflammation.
  • To evaluate the protective role of febuxostat against MTX-induced lung toxicity.

Main Methods:

  • Rats were divided into control, MTX-treated, and febuxostat-treated groups.
  • Lung tissues were analyzed histologically and immunohistochemically for inflammatory markers (iNOS, COX-2).
  • Oxidative stress markers, apoptosis, and inflammatory mediators (NF-kB, TNF-a, IL-1) were quantified.

Main Results:

  • MTX overdose led to lung inflammation, fibrosis, apoptosis, increased oxidative stress (MDA, GSH, SOD), and elevated inflammatory markers (NF-kB, IL-1, TNF-a, iNOS, COX-2).
  • Febuxostat treatment preserved lung architecture, reduced fibrosis, and mitigated oxidative stress and inflammation.
  • Febuxostat normalized iNOS and COX-2 levels, while NF-kB, IL-1, and TNF-a showed partial reduction.

Conclusions:

  • MTX overdose causes lung injury through oxidative stress, apoptosis, and sterile inflammation, leading to fibrosis.
  • Febuxostat demonstrates significant lung-protective effects against MTX-induced toxicity.
  • Febuxostat's protective mechanisms involve anti-inflammatory and antioxidant actions, preserving lung structure.