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Chronic Low-Dose Unsymmetrical Dimethylhydrazine Exposure in Rats: Multiorgan Mechanisms and Biomarker

Fuzhou Liu1, Bing Liu2, Keli Wang1

  • 1Department of General Medicine, PLA Rocket Force Characteristic Medical Center, Beijing, China.

Journal of Applied Toxicology : JAT
|November 28, 2025
PubMed
Summary

Chronic exposure to unsymmetrical dimethylhydrazine (UDMH) causes lung and kidney damage. Integrated multiomics identified hepatic Cyp4a1, serum taurine, and urinary L-DOPA as key biomarkers for UDMH toxicity.

Keywords:
biomarker discoverychronic toxicitymetabolomicstranscriptomicsunsymmetrical dimethylhydrazine

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Area of Science:

  • Toxicology
  • Biomarker Discovery
  • Systems Biology

Background:

  • Unsymmetrical dimethylhydrazine (UDMH) is a highly toxic rocket propellant with known adverse effects on multiple organs.
  • Characterizing the chronic low-dose toxicity of UDMH is crucial for risk assessment and safety protocols.

Purpose of the Study:

  • To investigate the organ-specific injury mechanisms and identify systemic biomarkers associated with chronic low-dose UDMH exposure.
  • To establish a mechanistic framework for UDMH toxicity using an integrated multiomics approach.

Main Methods:

  • Exploratory transcriptomics and metabolomics were employed in male Sprague-Dawley rats chronically exposed to UDMH.
  • Histopathological assessments were conducted to evaluate organ-specific injuries.
  • Integrated multiomics analysis was used to identify interconnected biomarkers.

Main Results:

  • Significant pulmonary injury, including hemorrhage and inflammation, and renal injury, indicated by tubular basophilia, were observed.
  • A biomarker triad was identified: hepatic Cyp4a1 upregulation (PPARα-mediated detoxification), elevated serum taurine (mitochondrial response), and increased urinary L-DOPA (neuroendocrine dysregulation).
  • These biomarkers collectively delineate UDMH pathophysiology, involving PPARα activation, mitochondrial stress, and catecholaminergic disruption.

Conclusions:

  • This study provides the first integrated multiomics framework for understanding chronic UDMH toxicity.
  • Hepatic Cyp4a1, serum taurine, and urinary L-DOPA are key indicators of UDMH-induced pathophysiology.
  • Findings highlight the potential for these biomarkers in future risk assessment strategies for UDMH exposure.