# Polyacrylic acid, but not polyethylene glycol, induces metabolic reprogramming linked to pulmonary fibrosis in rats

## TL;DR

Polyacrylic acid causes lung inflammation and fibrosis in rats, altering metabolism in ways linked to oxidative stress and mitochondrial dysfunction.

## Contribution

This study identifies systemic metabolic changes caused by polyacrylic acid exposure, linking them to pulmonary fibrosis mechanisms.

## Key findings

- A45 caused lung inflammation and fibrosis, while PEG did not.
- A45 altered amino acid, energy, and redox pathways, with specific metabolites like valine and leucine affected.
- Metabolomic profiling revealed enrichment in pathways related to collagen and energy demand.

## Abstract

Polyacrylic acids are widely used in industrial and consumer products, yet increasing evidence indicates that they can induce severe lung injury and rapidly progressing fibrosis. The underlying mechanisms remain unclear. In this study, we investigated the pulmonary toxicity of polyacrylic acid (A45) in comparison with polyethylene glycol (PEG, negative control) in a rat intratracheal instillation model. Lung inflammation and fibrosis were assessed up to 6 months. To explore systemic responses to pulmonary injury, serum metabolomics was performed using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). A45 exposure caused marked neutrophil infiltration, elevated inflammatory markers, and persistent fibrotic remodeling, while PEG induced no significant pulmonary changes. Metabolomic profiling detected 249 metabolites, of which 182 passed quality filtering. A45 significantly altered amino acid, energy, and redox pathways, whereas PEG showed minimal changes. Differential metabolites included valine, leucine, alanine, glutamine, malate, carnitine, cysteine, and methionine sulfoxide. Pathway analysis revealed enrichment of amino-acid/collagen-related and energy-demanding pathways. These findings demonstrate that polyacrylic acid induces systemic metabolic reprogramming linked to oxidative stress, mitochondrial dysfunction, and fibrosis, highlighting serum metabolomics as a valuable tool for mechanistic toxicology and biomarker discovery.

The online version contains supplementary material available at 10.1038/s41598-025-33213-1.