Toxicity studies with 5-hydroxymethylfurfural and its metabolite 5-sulphooxymethylfurfural in wild-type mice and transgenic mice expressing human sulphotransferases 1A1 and 1A2

Archives of Toxicology
Morana Bauer-MarinovicHansruedi Glatt

Abstract

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 ...Continue Reading

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Citations

Oct 12, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Benjamin SachseBernhard H Monien
Dec 22, 2015·Carbohydrate Polymers·Lionel LeclereCarine Michiels
Feb 12, 2013·Chemical Reviews·Robert-Jan van PuttenJohannes G de Vries
Oct 30, 2016·Regulatory Toxicology and Pharmacology : RTP·Ni LinHongtao Jin
Jul 22, 2016·Environmental Science and Pollution Research International·Duran Özkök, Sibel Silici
Apr 6, 2018·Chemistry Central Journal·Ummay Mahfuza ShaplaSiew Hua Gan
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Jan 26, 2020·Environmental Science and Pollution Research International·Khlood M El BohiMayada R Farag
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Apr 17, 2021·Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment·Yeison Fernando Barrios-RodríguezMaría Salomé Mariotti Celis
Jul 2, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Jing HuXia Li

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