Metabolomic studies on the systemic responses of mice with oxidative stress induced by short-term oxidized tyrosine administration

Oxidized tyrosine (O-Tyr) has attracted more interest in recent years because many researchers have discovered that it and its product (dityrosine) are associated with pathological conditions and metabolic disorders, especially various age-related disorders in biological systems. However, biochemical responses of an organism to short-term O-Tyr and dityrosine (Dityr) administration are unclear. Therefore, our objective is to provide insight into the effects of O-Tyr and Dityr administration on internal metabolic processes. In this study, three groups of Kunming mice were respectively given O-Tyr (320 mu g kg(-1) body weight), Dityr (320 mu g kg(-1) body weight) and sterile saline (control group) via gavage once daily for 7 consecutive days. We systematically analysed the O-Tyr and Dityr-induced metabonomic changes in mice serum and urine using proton nuclear magnetic resonance-based metabonomics approaches in conjunction with body weight, indices of oxidative damage, antioxidant capacity assessments, and antioxidant enzymes mRNA expressions. Compared with mice in the control group, O-Tyr and Dityr administration elevated oxidative damage to proteins and lipids, reduced antioxidant capacity, and suppressed antioxidant enzymes mRNA expression in mice. What's more, O-Tyr and DT administration can alter certain systemic metabolic processes in common, including enhanced fatty acid oxidation, glycolysis, glucose-alanine cycle, tricarboxylic acid (TCA) cycle metabolism, induced oxidative stress responses, elevated metabolism of vitamin-B-3, and altered gut microbiota functions. Our work provides a comprehensive view of the effects of O-Tyr and Dityr administration, implies an excess intake of oxidative proteins may result in deficiency of vitamin-B-3 in body, and reveals it is absolutely essential to avoid overly processed foods. These findings are very important for animal and human food safety.