Methoxyacetic acid exposure in rats induces N-butyrylglycinuria consistent with beta-oxidation impairment
Issued Date
2026-01-01
Resource Type
ISSN
03405761
eISSN
14320738
Scopus ID
2-s2.0-105037530936
Pubmed ID
42047697
Journal Title
Archives of Toxicology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Archives of Toxicology (2026)
Suggested Citation
Sala S., Kadyrov J., Bernal A., Castillo A.M., Naraprasertkul P., Paesalasakul N., Bekanan P., Dhitsuwon I., Kulthawatsiri T., Masuda R., Sharma M., Phetcharaburanin J., Car B.D., Contreras J.I.S., Lindon J.C., Wist J., Nicholson J.K., Holmes E. Methoxyacetic acid exposure in rats induces N-butyrylglycinuria consistent with beta-oxidation impairment. Archives of Toxicology (2026). doi:10.1007/s00204-026-04330-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116593
Title
Methoxyacetic acid exposure in rats induces N-butyrylglycinuria consistent with beta-oxidation impairment
Corresponding Author(s)
Other Contributor(s)
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 <sup>1</sup>H 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.