Toxicity studies with 5-hydroxymethylfurfural and its metabolite 5-sulphooxymethylfurfural in wild-type mice and transgenic mice expressing human sulphotransferases 1A1 and 1A2
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5-Sulphooxymethylfurfural (SMF), an electrophilic metabolite of the abundant Maillard product 5-hydroxymethylfurfural (HMF), was intraperitoneally administered to FVB/N mice. At a dosage of 250 mg/kg, most animals died after 5–11 days due to massive damage to proximal tubules. At lower dosages, administered repeatedly, tubules also were the major target of toxicity, with regeneration and atypical hyperplasia occurring at later periods. Additionally, hepatotoxic effects and serositis of peritoneal tissues were observed. SMF is a minor metabolite of HMF in conventional mice, but HMF is an excellent substrate for a major sulphotransferase (hSULT1A1) in humans. Parental FVB/N mice and FVB/N-hSULT1A1/2 mice, carrying multiple copies of the hSULT1A1/2 gene cluster, were exposed to HMF in drinking water (0, 134 and 536 mg/kg body mass/day) for 12 weeks. Nephrotoxic effects and enhanced proliferation of hepatocytes were only detected at the high dosage. They were mild and, surprisingly, unaffected by hSULT1A1/2 expression. Thus, SMF was a potent nephrotoxicant when administered as a bolus, but did not reach levels sufficient to produce serious toxicity when generated from HMF administered continuously via drinking water. This was even the case in transgenic mice expressing clearly higher HMF sulphation activity in liver and kidney than humans.
KeywordsNephrotoxicity Hepatotoxicity 5-Hydroxymethylfurfural 5-Sulphooxymethylfurfural Human sulphotransferases 1A1 and 1A2
We thank Ms. Swetlana König, Elisabeth Meyer and Elke Thom for excellent technical assistance, Dr. Gunhild Kozianowski (Südzucker AG, Mannheim, Germany) for a gift of HMF, and Drs. Albrecht Seidel and Heinz Frank (Biochemical Institute for Environmental Carcinogens, Prof. Dr. Gernot Grimmer Foundation, Grosshansdorf, Germany) for synthesizing SMF. This work has been carried out with support from the European Commission, Priority 5 on Food Quality and Safety (Contract no FOOD-CT-2003-506820 Specific Targeted Project), “Heat-generated food toxicants—identification, characterization and risk minimization”. This publication reflects the authors views and not necessarily those of the EC. The information in this document is provided as is and no guarantee or warranty is given that the information is fit for any particular purpose. The user thereof uses the information at his/her sole risk and liability.
Conflict of interest
Authors declare not having any financial or personal interest, nor having an association with any individuals or organizations that could have influenced inappropriately the submitted work.
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