Dietary Dityrosine Induces Mitochondrial Dysfunction by Diminished Thyroid Hormone Function in Mouse Myocardia

Abstract

Oxidized tyrosine products (OTP) have been detected in commercial foods with high protein content, such as meat and milk products. OTP intake induces tissue oxidative stress and affects the normal activity of the hypothalamic−pituitary−thyroid axis (HPT). This study aims to investigate the effects of OTP and their main product, dityrosine (Dityr), on mouse myocardial function and myocardial energy metabolism. Mice received daily intragastric administration of either tyrosine (Tyr; 420 μg/kg body weight), Dityr (420 μg/kg body weight), or OTP (1909 μg/kg body weight) for 35 days. Additionally, H9c2 cells were incubated with various concentrations of Dityr for 72 h. We found that OTP and pure Dityr induced oxidative stress in growing mice and in H9c2 cells, resulting in a redox state imbalance, myocardial injury, mitochondrial dysfunction, and energy metabolism disorder. Dityr interferes with T3 regulation of the myocardium via the PI3K/AKT/GSK3β pathway, leading to myocardial mitochondrial damage and energy metabolism disorders. Food-borne OTP, especially Dityr, can disrupt thyroid hormone function in mouse myocardia leading to mitochondrial dysfunction, energy metabolism disorder, and oxidative stress.

Effects of oxidized rice bran protein induced by rancidity on the hepatic function in mice

“…The inhibition of the Nrf2 pathway was also observed in mouse myocardia treated with oxidized tyrosine products, which might also lead to more formation of ROS, exacerbating oxidative stress. 14 In the kidneys, excessively oxidized RBP significantly elevated the expression of Nrf2, GPX-4, and HO-1, 23 indicating oxidized RBP caused organ damage via a different mechanism. In addition, Nrf2 can remove the abnormal proteins that might interfere with cellular functions.…”

“…11,12,25 However, most research studies covered the health effects of oxidized animal-based proteins. 14,15,26,27 Owing to different amino acid profiles, different storage and…”

“…11,12,25 However, most research studies covered the health effects of oxidized animal-based proteins. 14,15,26,27 Owing to different amino acid profiles, different storage and processing conditions, and the presence of unique micronutrients, evaluating the nutritional value of oxidized plant protein is of great significance. RBP is a premium protein that presents excellent nutritional and pharmaceutical potential.…”

“…10,12 Large-scale literature has investigated the impact of oxidative modification on the nutritional value of animal-based protein, while little attention has been paid to the nutritional value of oxidized plant protein. [13][14][15] In addition to the different amino acid profiles, less fat content and higher polyphenol content can improve the antioxidant capacities of plant protein, 3,16 which might pose different implications on the body than animal-based protein. However, the impact and the related mechanism of oxidation on the nutritional value of plant protein remain to be elucidated.…”

Sodium butyrate protects against oxidative stress in high‐fat‐diet‐induced obese rats by promoting GSK‐3β/Nrf2 signaling pathway and mitochondrial function

“…Mitochondrial function is a crucial regulator of whole‐body metabolism. Mn‐SOD and GSH‐Px represent important antioxidant enzymes in the mitochondria, where they play essential roles in maintaining mitochondrial redox homeostasis (AlAmri et al, 2020; Lu et al, 2020). Additionally, acetyl‐CoA and NADH/NAD + ratios are the major indicators of mitochondrial energy metabolism.…”