Related Experiment Video
Updated: Apr 23, 2026
An Integrated Workflow of Identification and Quantification on FDR Control-Based Untargeted Metabolome
Published on: September 20, 2022
Discovery of systematic responses and potential biomarkers induced by ochratoxin A using metabolomics
1a Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering , China Agricultural University , Beijing , China.
Abstract:
Ochratoxin A (OTA) is known to be nephrotoxic and hepatotoxic in rodents when exposed orally. To understand the systematic responses to OTA exposure, GC-MS- and (1)H-NMR-based metabolomic techniques together with histopathological assessments were applied to analyse the urine and plasma of OTA-exposed rats. It was found that OTA exposure caused significant elevation of amino acids (alanine, glycine, leucine etc.), pentose (ribose, glucitol, xylitol etc.) and nucleic acid metabolites (pseudouridine, adenosine, uridine). Moreover, myo-inositol, trimethylamine-oxide (TMAO), pseudouridine and leucine were identified as potential biomarkers for OTA toxicity. The primary pathways included the pentose phosphate pathway (PPP), the Krebs cycle (TCA), the creatine pathway and gluconeogenesis. The activated PPP was attributed to the high requirements for nicotinamide adenine dinucleotide phosphate (NADPH), which is involved in OTA metabolism through cytochrome P450. The elevated gluconeogenesis and TCA suggest that energy metabolism was involved. The up-regulated synthesis of creatinine reveals the elevated catabolism of proteins. These findings provide an overview of systematic responses to OTA exposure and metabolomic insight into the toxicological mechanism of OTA.
Insights
Ochratoxin A (OTA) exposure in rats alters amino acid, pentose, and nucleic acid metabolism. Researchers identified key biomarkers and metabolic pathways involved in OTA toxicity, offering insights into its toxicological mechanisms.
Area of Science:
- Toxicology
- Metabolomics
- Biochemistry
Background:
- Ochratoxin A (OTA) is a mycotoxin known for its nephrotoxic and hepatotoxic effects in rodents.
- Understanding the systemic metabolic responses to OTA exposure is crucial for elucidating its toxicological mechanisms.
Purpose of the Study:
- To investigate the systematic metabolic alterations in rats following oral Ochratoxin A exposure.
- To identify potential biomarkers and key metabolic pathways associated with OTA toxicity using metabolomic approaches.
Main Methods:
- GC-MS and (1)H-NMR based metabolomic analyses were performed on urine and plasma samples from OTA-exposed rats.
- Histopathological assessments were conducted to complement the metabolomic findings.
- Data analysis focused on identifying significant changes in metabolite levels and affected metabolic pathways.
Main Results:
- OTA exposure led to significant elevations in amino acids, pentose metabolites, and nucleic acid metabolites.
- Myo-inositol, trimethylamine-N-oxide (TMAO), pseudouridine, and leucine were identified as potential biomarkers for OTA toxicity.
- Key affected pathways included the pentose phosphate pathway (PPP), Krebs cycle (TCA), creatine pathway, and gluconeogenesis, indicating altered energy metabolism and protein catabolism.
Conclusions:
- Metabolomic profiling reveals significant systemic metabolic disruptions following Ochratoxin A exposure.
- The study identifies novel biomarkers and elucidates the involvement of energy metabolism and oxidative stress pathways in OTA toxicogenesis.
- These findings provide a comprehensive overview of the toxicological mechanisms of OTA.
