A pioneer study on human 3-nitropropionic acid intoxication: Contributions from metabolomics

Area of Science:

• Biochemistry
• Toxicology
• Metabolomics

Background:

• 3-nitropropionic acid (3-NPA) is a neurotoxin inhibiting succinate dehydrogenase, affecting cellular energy production.
• Human 3-NPA intoxication presents with a range of symptoms from gastrointestinal distress to severe neurological impairment, including coma and death.

Purpose of the Study:

• To investigate the metabolic consequences of 3-NPA intoxication in a human patient.
• To identify biomarkers and understand the body's response to 3-NPA exposure.

Main Methods:

• Liquid chromatography-Orbitrap mass spectrometry-based metabolomics analysis.
• Analysis of plasma, urine, and cerebrospinal fluid (CSF) samples.

Main Results:

• Successfully identified 3-NPA in patient samples, confirming intoxication.
• Detected significant alterations in 80, 160, and 62 metabolites in plasma, urine, and CSF, respectively.
• Observed evidence of protective mechanisms, oxidative stress, and energy disruption.

Conclusions:

• This is the first reported case of 3-NPA intoxication in Norway and the first human metabolomics study of its kind globally.
• The findings underscore the necessity for healthcare providers to consider toxin-induced metabolic derangements in differential diagnoses.
• Metabolomics provides valuable insights into the complex systemic effects of neurotoxins.