Potential protective effect of 3,3'-methylenebis(1-ethyl-4-hydroxyquinolin-2(1H)-one) against bleomycin-induced lung injury in male albino rat via modulation of Nrf2 pathway: biochemical, histological, and immunohistochemical study

Naunyn Schmiedebergs Arch Pharmacol. 2023 Apr;396(4):771-788. doi: 10.1007/s00210-022-02324-1. Epub 2022 Dec 8.

Abstract

Acute lung injury is a serious condition accounting for the majority of acute respiratory failure. Bleomycin (BLM) is an antibiotic that was first described as a chemotherapeutic agent. 3,3'-methylenebis(1-ethyl-4-hydroxyquinolin-2(1H)-one) was reported to have anti-inflammatory, anti-apoptotic, and anti-oxidative properties. The current work aimed to assess the possible protective effects and the mechanism of protection of 3,3'-methylenebis-(1-ethyl-4-hydroxyquinolin-2(1H)-one) on BLM-induced lung injury in addition to the effect and underlying mechanisms of nuclear factor-erythroid-related factor 2 pathway against this injury. Rats were equally divided into four groups: control group, BLM group, 1-ethyl-4-hydroxyquinolin-2(1H)-one-treated group, and BLM with 1-ethyl-4-hydroxyquinolin-2(1H)-one-treated group. At the end of the work, the blood samples were proceeded for biochemical study. Lung specimens were obtained for biochemical, histological, and immunohistochemical study. The results exhibited a significant increase in both malondialdehyde and tumor necrotic factor-α with a significant decrease in glutathione, superoxide dismutase, IL 10, surfactant protein A, and nuclear factor erythroid 2-related factor 2 in BLM group. The lung histological results showed various morphological changes in the form of disturbed architecture, inflammatory cell infiltration, and intraluminal debris. This group also displayed a significant increase in the mean surface area fraction of anti-cleaved caspase 3, while group IV exhibited amelioration in the previously mentioned parameters and histological alternations that were induced by BLM. It could be concluded that 3,3'-methylenebis(1-ethyl-4-hydroxyquinolin-2(1H)-one) has anti-oxidative, anti-inflammatory, and anti-apoptotic protective effects against BLM-induced lung injury.

Keywords: 3,3′-Methylenebis; Bleomycin; Lung injury; Nrf2 pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury* / pathology
  • Animals
  • Bleomycin / toxicity
  • Lung
  • Male
  • NF-E2-Related Factor 2 / metabolism
  • Pulmonary Fibrosis* / chemically induced
  • Pulmonary Fibrosis* / drug therapy
  • Pulmonary Fibrosis* / prevention & control
  • Rats

Substances

  • Bleomycin
  • NF-E2-Related Factor 2
  • 4-hydroxyquinolin-2(1H)-one