Rapid and complete urinary elimination of [¹⁴C]‐5‐hydroxymethyl‐2‐furaldehyde administered orally or intravenously to rats

Abstract

5-Hydroxymethyl-2-furaldehyde (HMF), is a major product of sugar degradation found in food and solutions used in parenteral nutrition. Labeled [14C]HMF was synthesized by dehydration of [14C]fructose on ion-exchange resin and administered per os (po) and intravenously (iv) to rats. Metabolic balance of radioactivity demonstrated that HMF or its metabolites are rapidly eliminated in the urine with a recovery of 95-100% after 24 h. Literature reported, in some cases, 50% retention in the body. HMF was completely converted to two metabolites, which have been identified by nuclear magnetic resonance (NMR) and mass spectroscopy (MS) as 5-hydroxymethyl-2-furoic acid and N-(5-hydroxymethyl-2-furoyl)glycine. Administration of high doses of HMF showed a similar rapid elimination, but a proportional reduction of the amount of the glycine conjugate produced. Whole-animal-body autoradiography confirm that shortly after administration radioactive material was present in the liver but was mostly in the kidney and the bladder. The only significant difference between po and iv administration was the presence of a higher level of radioactive material in the brain of iv-treated rats.

5-Hydroxymethyl-2-Furfural (HMF) – Heat-Induced Formation, Occurrence in Food and Biotransformation - a Review

“…Excretion of HMF was primarily via urine with an efficiency of 60-80% of administered HMF excreted by this route within 48 h. The increased level of HMF-derived radioactivity was observed in the liver and kidney. Similar results were obtained by Germond et al [1987] in their study performed also with radiolabelled [ 14 C]-HMF in rats. The authors demonstrated that HMF or its metabolites were rapidly eliminated in the urine with a recovery of 95-100% after 24 h. They postulated that HMF was excreted in rat urine mainly as HMFA and its glycine conjugate N-(5-hydroxymethyl-2-furoyl)-glycine (HMFG).…”

“…However, Jellum et al [1973] could not find HMFG (the glycine conjugate of HMFA) in urine because they performed ether extracts on acidified urine and HMFG is not soluble in ether. Interestingly, that increasing HMF dose results in increasing of an HMFA/HMFG ratio [Germond et al, 1987]. This may suggest that HMFG formation is impeded by the availability of free glycine.…”

Renal organic anion transporters OAT1 and OAT3 mediate the cellular accumulation of 5-sulfooxymethylfurfural, a reactive, nephrotoxic metabolite of the Maillard product 5-hydroxymethylfurfural

“…The principal urinary metabolites are 5-hydroxymethyl-2-furoic acid and its glycine conjugate and furan-2,5-dicarboxylic acid [19][20][21]. SMF was not detected in urine.…”

Metabolic Transit and in vivo Effects of Melanoidins and Precursor Compounds Deriving from the Maillard Reaction

“…The only balance study carried out so far was performed in rats which were fed on 14 C-labeled 5-hydroxymethyl-2-furaldehyde (HMF). In that study, the administered radiolabeled HMF accumulated mostly in the kidneys and less in the bladder and liver [28].…”