Temporal Dynamics of Oxidative Stress and Inflammation in Bronchopulmonary Dysplasia

Int J Mol Sci. 2024 Sep 21;25(18):10145. doi: 10.3390/ijms251810145.

Abstract

Bronchopulmonary dysplasia (BPD) is the most common lung complication of prematurity. Despite extensive research, our understanding of its pathophysiology remains limited, as reflected by the stable prevalence of BPD. Prematurity is the primary risk factor for BPD, with oxidative stress (OS) and inflammation playing significant roles and being closely linked to premature birth. Understanding the interplay and temporal relationship between OS and inflammation is crucial for developing new treatments for BPD. Animal studies suggest that OS and inflammation can exacerbate each other. Clinical trials focusing solely on antioxidants or anti-inflammatory therapies have been unsuccessful. In contrast, vitamin A and caffeine, with antioxidant and anti-inflammatory properties, have shown some efficacy, reducing BPD by about 10%. However, more than one-third of very preterm infants still suffer from BPD. New therapeutic agents are needed. A novel tripeptide, N-acetyl-lysyltyrosylcysteine amide (KYC), is a reversible myeloperoxidase inhibitor and a systems pharmacology agent. It reduces BPD severity by inhibiting MPO, enhancing antioxidative proteins, and alleviating endoplasmic reticulum stress and cellular senescence in a hyperoxia rat model. KYC represents a promising new approach to BPD treatment.

Keywords: anti-inflammatory; antioxidant; bronchopulmonary dysplasia; endoplasmic reticulum stress; inflammation; oxidative stress; senescence; temporal relationship; therapeutic intervention.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Bronchopulmonary Dysplasia* / drug therapy
  • Bronchopulmonary Dysplasia* / metabolism
  • Bronchopulmonary Dysplasia* / pathology
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Inflammation* / drug therapy
  • Inflammation* / metabolism
  • Oxidative Stress* / drug effects
  • Rats

Substances

  • Antioxidants
  • Anti-Inflammatory Agents