Relationship between HMF intake and SMF formation in vivo: An animal and human study
Silvia Pastoriza de la Cueva1, Juana Álvarez1, Ákos Végvári2
1Departamento de Nutrición y Bromatología, Facultad de Farmacia, Universidad de Granada, Granada, Spain.
Scope:
5-Hydroxymethylfurfural (HMF) is a furanic compound produced in heat-processed foods by nonenzymatic browning reactions. HMF has been demonstrated to be hepato- and nephrotoxic in animals with a link to its metabolite 5-sulfooxymethylfurfural (SMF). To date little is known about either the formation of SMF from ingested HMF or the formation of DNA adducts in animals or human beings.
Methods And Results:
To assess SMF in vivo formation, we first performed a study in mice treated with high/low doses of oral HMF. We found increased concentrations of SMF in plasma and DNA SMF-adducts in leukocytes, hepatic tissue, and kidneys by means of LC-MS/MS, but no spatial formation in such tissues was observed by MALDI-MS imaging technology due to low sensitivity. In a second experiment, we measured the exposure to HMF in a Spanish preadolescent population. We analyzed the concentration of HMF metabolites (plasma, urine) and measured, for the first time, the presence of SMF in plasma and DNA SMF-adducts in leukocytes.
Conclusion:
This study provides the first evidence that oral HMF is readily transformed into SMF in vivo, giving rise to the formation of DNA adducts in a direct relation with HMF intake, both in animals and human beings.
Insights
Oral 5-hydroxymethylfurfural (HMF) readily forms the toxic metabolite 5-sulfooxymethylfurfural (SMF) in vivo. This study confirms SMF formation and DNA adducts in animals and humans, linking HMF intake to potential health risks.
Area of Science:
- Food Chemistry
- Toxicology
- Metabolomics
Background:
- 5-Hydroxymethylfurfural (HMF) is a food processing byproduct linked to hepato- and nephrotoxicity.
- Its metabolite, 5-sulfooxymethylfurfural (SMF), is suspected to mediate toxicity, but its in vivo formation and DNA adduct potential were unknown.
Purpose of the Study:
- To investigate the in vivo formation of SMF from ingested HMF.
- To determine if SMF forms DNA adducts in animals and humans.
- To assess HMF metabolite exposure in a human population.
Main Methods:
- Mice were administered oral HMF, and plasma and tissue samples were analyzed for SMF and DNA adducts using LC-MS/MS.
- MALDI-MS imaging was used to assess spatial formation of SMF.
- HMF metabolites, including SMF and DNA adducts, were measured in plasma and urine of Spanish preadolescents.
Main Results:
- Oral HMF administration led to increased plasma SMF concentrations and DNA SMF-adducts in mouse leukocytes, liver, and kidneys.
- MALDI-MS imaging lacked sensitivity to detect spatial SMF formation.
- SMF and DNA SMF-adducts were detected in plasma and leukocytes of the human cohort, correlating with HMF intake.
Conclusions:
- This study provides the first evidence that ingested HMF is converted to SMF in vivo.
- The formation of DNA adducts is directly related to HMF intake in both animal models and humans.
- Findings highlight potential health risks associated with HMF exposure from processed foods.
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