Methoxyacetic acid exposure in rats induces N-butyrylglycinuria consistent with beta-oxidation impairment
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Methoxyacetic acid (MAA) is a testicular toxin that targets spermatocytes and round spermatids by disrupting mitochondrial function, leading to cellular energy depletion. Male Sprague-Dawley rats were given single oral doses of MAA (150 or 650 mg/kg), resulting in no mortality but transient toxicity signs and modest body weight effects, especially at the higher dose. Histopathology revealed dose- and time-dependent testicular damage, with selective germ cell necrosis by 48 h and extensive germ cell loss, spermatic giant cells, and epididymal inflammation observed in high-dose animals by 168 h. Metabolic analysis using high resolution 1H NMR spectroscopy and OPLS-DA identified elevated urinary excretion of N-butyryl glycine, a marker of mitochondrial dysfunction and impaired β-oxidation. The persistence of N-butyryl glycine and altered energy metabolites up to 168 h indicates sustained mitochondrial stress and disruption of ATP-dependent processes essential for spermatogenesis. Moreover, the close structural similarity between MAA and butyrate raises the possibility that MAA interacts directly with enzymes involved in butyryl-CoA turnover during the terminal steps of β-oxidation in rodents.
Date Issued
2026-08-01
Date Acceptance
2026-02-05
Citation
Archives of Toxicology, 2026, 100 (8), pp.3507-3518
ISSN
0340-5761
Publisher
Springer
Start Page
3507
End Page
3518
Journal / Book Title
Archives of Toxicology
Volume
100
Issue
8
Copyright Statement
© The Author(s) 2026. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1007/s00204-026-04330-1
Subjects
Methoxyacetic acid
MAA
Urine
NMR
Metabolomics
Metabonomics
Publication Status
Published
Date Publish Online
2026-04-28