Work

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

Year: 2025

Type: article

Abstract: ABSTRACT Unsymmetrical dimethylhydrazine (UDMH), a highly toxic rocket propellant with known multiorgan effects, requires urgent characterization of its chronic low‐dose toxicity. Using an integrated approach including exploratory transcriptomics ( n = 3/group) and metabolomic ( n = 4/group) approaches in male Sprague–Dawley rats exposed to high‐dose UDMH concentrations (100 ppm (v/v), 4 h/day, 5 days/week for 60 days), we delineated organ‐specific injury mechanisms and identified candidate systemic biomarkers. Histopathological assessment revealed significant pulmonary injury (62.5% incidence of focal hemorrhage, p = 0.015; inflammatory focus density: 8.3 ± 1.7 foci/mm 2 ) and renal injury (tubular basophilia index: 1.8 ± 0.4, p < 0.001). Integrated multiomics analysis identified a mechanistically interconnected biomarker triad: (1) hepatic Cyp4a1 upregulation (log 2 FC = 4.7), indicating PPARα‐mediated adaptive detoxification; (2) elevated serum taurine (1.27‐fold, p < 0.05), reflecting mitochondrial compensatory responses; and (3) increased urinary L‐DOPA (3.1‐fold, false discovery rate [FDR] < 0.05), signifying neuroendocrine dysregulation. Together, these core biomarkers delineate the pathophysiology of chronic UDMH toxicity, characterized by PPARα‐driven detoxification intersecting with mitochondrial stress adaptation and catecholaminergic disruption across organ systems. To our knowledge, this is the first integrated multiomics study of chronic UDMH exposure, establishing a mechanistic framework for toxicity and highlighting pulmonary–renal pathology, serum taurine, and hepatic Cyp4a1 as key indicators for developing future risk assessment strategies.

Source: Journal of Applied Toxicology

DOI: 10.1002/jat.70008