Health Effects of Dietary Oxidized Tyrosine and Dityrosine Administration in Mice with Nutrimetabolomic Strategies

Abstract

This study aims to investigate the health effects of long-term dietary oxidized tyrosine (O-Tyr) and its main product (dityrosine) administration on mice metabolism. Mice received daily intragastric administration of either O-Tyr (320 μg/kg body weight), dityrosine (Dityr, 320 μg/kg body weight), or saline for consecutive 6 weeks. Urine and plasma samples were analyzed by NMR-based metabolomics strategies. Body weight, clinical chemistry, oxidative damage indexes, and histopathological data were obtained as complementary information. O-Tyr and Dityr exposure changed many systemic metabolic processes, including reduced choline bioavailability, led to fat accumulation in liver, induced hepatic injury, and renal dysfunction, resulted in changes in gut microbiota functions, elevated risk factor for cardiovascular disease, altered amino acid metabolism, induced oxidative stress responses, and inhibited energy metabolism. These findings implied that it is absolutely essential to reduce the generation of oxidation protein products in food system through improving modern food processing methods.

Intake of Oxidized Proteins and Amino Acids and Causative Oxidative Stress and Disease: Recent Scientific Evidences and Hypotheses

“…Particular protein oxidation products, such as protein carbonyls, the α‐amino adipic acid, tyrosine, tryptophan, and phenylalanine oxidation products, among others, initially exposed to the intestinal mucosa, are absorbed and hence, accumulate in the epithelium and may be distributed to distant internal organs through the bloodstream (Ding, Cheng et al., , Ding, Li et al., ; Wang et al., ; Yang, Zhang et al., , Yang, Yan et al., ). The intestinal uptake of specific protein oxidation products after oral administration, and the subsequent organic accumulation proves the bioavailability and bioactivity of these species which seem to have certain tropism for target tissues.…”

“…The intestinal uptake of specific protein oxidation products after oral administration, and the subsequent organic accumulation proves the bioavailability and bioactivity of these species which seem to have certain tropism for target tissues. This is the case of protein carbonyls for the intestinal epithelium (Keshavarzian et al., ), the α‐amino adipic acid for pancreas (Wang et al., ), and oxidized tyrosines for pancreas, kidney and liver (Ding, Cheng et al., ; Ding, Li et al., ; Ding, Tang et al., ; Yang, Zhang et al., , Yang, Yan et al., ). Finally, it is worth noting that the elevation of protein oxidation markers in blood and tissues may not only be caused by the intake of such species.…”

“…Other pathological mechanisms may involve exacerbated antioxidant and immune responses, which facilitate chronic inflammation and tissue degeneration (Keshavarzian et al., ). Proteomic, genomic, and metabolomics studies have recently observed the ability of oxidized amino acids to modulate gene expression, leading to impaired physiological functions (Li, Shi, Le, Ding, & Zhao, ; Yang, Zhang et al., ; Yang, Yan et al., ,). Finally, animal proteins, heme iron and derived protein oxidation products may alter the microbiome, making the intestinal mucosa more sensitive to both biological and chemical threats (Constante, Fragoso, Calvé, Samba‐Mondonga, & Santos, ; Portune et al., ; Van der Leek, Yanishevsky, & Kozyrskyj, ).…”

“…Yang, Zhang et al. () provided an oral daily dose of 320 μg/kg bw/day of dityrosine via gavage for 7 consecutive days. Systemic oxidative stress was manifested with elevated plasma levels of lipid and protein oxidation markers and reduced synthesis and activity of endogenous antioxidant enzymes.…”

Benefits of wine‐based marination of strip steaks prior to roasting: inhibition of protein oxidation and impact on sensory properties

“…A relatively new study identified certain tyrosine and tryptophan oxidation products as discriminating metabolites during digestion of red meat versus white meat, suggesting that these species may play a still unclear role in the pathogenesis of these disorders. A recent review and several original articles emphasized the role of assorted protein oxidation products, including protein carbonyls, oxidized tryptophan, and dityrosines, on various health disorders …”