Effects of Dityrosine Administration on Myocardial Function and Energy Metabolism in Mice

Center For Food Nutrition and Functional Food Engineering , School of Food Science and Technology, Wuxi,214122

Abstract： Objective: To study the effects of oxidized tyrosine products and dityrosine on myocardial function and energy metabolism in 10-week-gavaged mice. Methods: 30 Female Kunming mice were assigned to three groups: gavaged with saline (Con), oxidized tyrosine products (O-Tyr) and dityrosine (Dityr) for 320 μg/kg • bw for 10 weeks. Levels of oxidized protein products (DT, AOPPs, 3-NT) and lipid peroxidation products (MDA), oxidative stress（T-AOC and GSH/GSSG), markers of myocardium injury (CK, CK-MB, cTnI and LDH), the activities of Na+-K+ ATPase, Ca2+-ATPase, LDH in myocardium, level of FFA, markers of inflammatory factor (CRP and TNF-α) in mice plasma and myocardium were investigated and the genes related to inflammatory response and energy metabolism were detected by Real-time quantitative (PCR). Results: 10 weeks of gavage experiments enhanced the levels of dityrosine (DT), advanced oxidation protein products (AOPPs), 3-nitrotyrosine (3-NT), and malondialdehyde (MDA) in mice plasma and myocardium, and decreased total antioxidant capacity(T-AOC) and the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) in mice plasma and myocardium. Besides, O-Tyr and Dityr increased the levels of creatine kinase (CK), creatine kinase isoenzymes (CK-MB) , cardiac troponin I (cTnI), lactate dehydrogenase (LDH) in plasma , increased the levels of free fatty acids(FFA) in plasma and myocardium, and decreased the activities of Na+-K+ ATPase, Ca2+-ATPase, LDH in myocardium; O-Tyr and Dityr increased the levels of C-reactive protein (CRP) and tumour necrosis factor α (TNF-α) in plasma; The gene expression of inflammatory response were up-regulated. The gene expression of energy metabolism were shifted(AMPK, PPARα, CPT-I, PFK1, CS, ogdh.etc). Conclusion: Our findings reveal that O-Tyr and Dityr increase the accumulation of myocardial protein oxidation and lipid peroxidation products and induce oxidative damage to myocardium. O-Tyr and Dityr may cause myocardial tissue injury and inflammatory response. O-Tyr and Dityr lead to myocardial energy metabolism disorders, affecting myocardial function. Dityrosine, as the main component of tyrosine oxidative products, may play a major role in the process of oxidized tyrosine products causing myocardial injury in mice. in mice plasma.

Keywords： oxidized tyrosine dityrosine oxidative stress energy metabolism myocardial function