Logo image
Back
Methoxyacetic acid exposure in rats induces N-butyrylglycinuria consistent with beta-oxidation impairment
Journal article   Open access

Methoxyacetic acid exposure in rats induces N-butyrylglycinuria consistent with beta-oxidation impairment

Samuele Sala, Janonna Kadyrov, Andrés Bernal, Andres M. Castillo, Preechaya Naraprasertkul, Nadia Paesalasakul, Proud Bekanan, Issariya Dhitsuwon, Thanaporn Kulthawatsiri, Reika Masuda, …
Archives of Toxicology
2026
DOI: https://doi.org/10.1007/s00204-026-04330-1
pdf
exposure in rats1.65 MBDownloadView
Open Access CC BY V4.0

Abstract

Methoxyacetic acid MAA Urine NMR Metabolomics Metabonomics
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.

Details

Metrics

1 Record Views
Logo image