关键词: 酪氨酸氧化产物；双酪氨酸；氧化应激；心肌损伤；能量代谢障碍

Abstract: Food-borne tyrosine oxidation product (OTP) not only affects the quality and nutritional value of foods, but also has potential harm to the health of the body; but the relevant mechanism is not yet clear. In this study, we investigated the effects of OTP and dityrosine (DT) as an OTP component on redox homeostasis and myocardial function in mice and elucidated the underlying mechanisms. Thirty male C57BL/6 mice were randomly divided into 3 groups: control, OTP and DT groups. The animals in these groups were intragastrically administered with 420 μg/kg mb tyrosine solution, 1 909 μg/kg mb OTP and 420 μg/kg mb DT solution, respectively, for 35 consecutive days. Weekly changes in body mass were monitored during this period. After that, redox homeostasis parameters, antioxidant enzyme activities and mitochondrial energy metabolism in plasma and myocardium were determined. The results showed that compared with the control group, gavage administration of OTP and DT resulted in a significant increase in cardiac index and the levels of myocardial reactive oxygen species (ROS), DT, malondialdehyde, and free fatty acids (P < 0.05), a significant decrease in total antioxidant capacity, acetyl-CoA content, NADH/NAD+ and ATPase levels (P < 0.05), and a significant increase in plasma tumor necrosis factor α, creatine kinase, and lactate dehydrogenase levels (P < 0.05). Real-time polymerase chain reaction (PCR) results showed that compared with the control group, the mRNA expression levels of anti-oxidation-related genes such as Pi3k, Ampk, Nrf2 and Nqo1 and mitochondrial synthesis-related genes such as Pgc1α, Tfam and Pparα in mice in the DT and OTP groups were significantly down-regulated (P < 0.05). In addition, the effects of DT on myocardial oxidative stress and energy metabolism was consistent with that of OTP with no significant difference between them (P > 0.05). The above findings show that OTP and DT can cause myocardial oxidative stress in mice, leading to myocardial injury and energy metabolism disorder. DT is the major component of OTP that plays a key role in inducing myocardial injury.

Key words: tyrosine oxidation product; dityrosine; oxidative stress; myocardial damage; energy metabolism disorder