Fate of Sulfonamides and Tetracyclines in Meat during Pan Cooking: Focus on the Thermodegradation of Sulfamethoxazole.

Although antimicrobials are generally found in trace amounts in meat, the human health risk they bear cannot be ignored. With the ultimate aim of making a better assessment of consumer exposure, this study explored the effects of pan cooking on sulfonamides and tetracyclines in meat. Screening of these antimicrobials in cooked meat was first performed by the European Union Reference Laboratory on the basis of HPLC-MS/MS analyses. A proof of concept approach using radiolabeling was then carried out on the most cooking-sensitive antimicrobial-sulfamethoxazole-to assess if a thermal degradation could explain the observed cooking losses. Degradation products were detected thanks to separation by HPLC and monitoring by online radioactivity detection. HPLC-Orbitrap HRMS analyses completed by 1D and 2D NMR experiments allowed the structural characterization of these degradation compounds. This study revealed that cooking could induce significant antimicrobial losses of up to 45% for sulfamethoxazole. Six potential degradation products of 14C-sulfamethoxazole were detected in cooked meat, and a thermal degradation pattern was proposed. This study highlights the importance of considering the cooking step in chemical risk assessment procedures and its impact on the level of chemical contaminants in meat and on the formation of potentially toxic breakdown compounds.

Towards Aldehydomics: Untargeted Trapping and Analysis of Reactive Diet-Related Carbonyl Compounds Formed in the Intestinal Lumen.

Lipid peroxidation and subsequent formation of toxic aldehydes, such as 4-hydroxynonenal, is known to be involved in numerous pathophysiological processes, possibly including the development of colorectal cancer. This work aimed at the development of an untargeted approach using high-performance liquid chromatography coupled with high-resolution mass spectrometry (HPLC-HRMS) for tracking aldehydes in both suspect screening and untargeted methods in fecal water, representing the aqueous environment of colon epithelial cells. This original approach is based on the introduction of a characteristic isotopic labeling by selective derivatization of the carbonyl function using a brominated reagent. Following a metabolomics workflow, the developed methodology was applied to the characterization of aldehyde compounds formed by lipid peroxidation in rats fed two different diets differentially prone to lipoperoxidation. Derivatized aldehydes were first selectively detected on the basis of their isotopic pattern, then annotated and finally identified by tandem mass spectrometry. This original approach allowed us to evidence the occurrence of expected aldehydes according to their fatty acid precursors in the diet, and to characterize other aldehydes differentiating the different diets.

Heme-Iron-Induced Production of 4-Hydroxynonenal in Intestinal Lumen May Have Extra-Intestinal Consequences through Protein-Adduct Formation.

Some epidemiological studies show that heme iron consumption, in red meat, is associated to the development of several chronic diseases, including cancers and cardio-metabolic diseases. As heme iron intestinal absorption is finely regulated, we hypothesized that heme iron may act indirectly, through the peroxidation of dietary lipids, in food or in the intestinal lumen during digestion. This heme-iron-induced lipid peroxidation provokes the generation of toxic lipid oxidation products that could be absorbed, such as 4-hydroxynonenal (HNE). In a first experiment, heme iron given to rats by oral gavage together with the linoleic-acid-rich safflower oil induced the formation of HNE in the intestinal lumen. The HNE major urinary metabolite was elevated in the urine of the treated rats, indicating that this compound has been absorbed. In a second experiment, we showed that stable isotope-labeled HNE given orally to rats was able to reach non-intestinal tissues as a bioactive form and to make protein-adducts in heart, liver and skeletal muscle tissues. The presence of HNE-protein adducts in those tissues suggests a putative biological role of diet-originating HNE in extra-intestinal organs. This finding could have major consequences on the onset/development of chronic diseases associated with red meat over-consumption, and more largely to peroxidation-prone food consumption.

Lactose and Fructo-oligosaccharides Increase Visceral Sensitivity in Mice via Glycation Processes, Increasing Mast Cell Density in Colonic Mucosa.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and erratic bowel habits. A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) can reduce symptoms of IBS, possibly by reducing microbial fermentation products. We investigated whether ingestion of FODMAPs can induce IBS-like visceral hypersensitivity mediated by fermentation products of intestinal microbes in mice. METHODS: C57Bl/6 mice were gavaged with lactose, with or without the antiglycation agent pyridoxamine, or saline (controls) daily for 3 weeks. A separate group of mice were fed a diet containing fructo-oligosaccharides, with or without pyridoxamine in drinking water, or a normal chow diet (controls) for 6 weeks. Feces were collected and analyzed by 16S ribosomal RNA gene sequencing and bacterial community analyses. Abdominal sensitivity was measured by electromyography and mechanical von Frey filament assays. Colon tissues were collected from some mice and analyzed by histology and immunofluorescence to quantify mast cells and expression of advanced glycosylation end-product specific receptor (AGER). RESULTS: Mice gavaged with lactose or fed fructo-oligosaccharides had increased abdominal sensitivity compared with controls, associated with increased numbers of mast cells in colon and expression of the receptor for AGER in proximal colon epithelium. These effects were prevented by administration of pyridoxamine. Lactose and/or pyridoxamine did not induce significant alterations in the composition of the fecal microbiota. Mass spectrometric analysis of carbonyl compounds in fecal samples identified signatures associated with mice given lactose or fructo-oligosaccharides vs controls. CONCLUSIONS: We found that oral administration of lactose or fructo-oligosaccharides to mice increases abdominal sensitivity, associated with increased numbers of mast cells in colon and expression of AGER; these can be prevented with an antiglycation agent. Lactose and/or pyridoxamine did not produce alterations in fecal microbiota of mice. Our findings indicate that preventing glycation reactions might reduce abdominal pain in patients with IBS with sensitivity to FODMAPs.