The team of Professor Chen Wei from Zhejiang University published a paper in Redox Biology to reveal the toxicity mechanism of urethane, a potentially harmful substance in fermented food

Recently, Professor Chen Wei's team from the School of Biosystems Engineering and Food Science , Zhejiang University published a research paper "Ethyl carbamate triggers ferroptosis in liver through inhibiting GSH synthesis and suppressing Nrf2" in the top international journal "Redox Biology" (IF5 1038) in the field of free radical biology

This study revealed the mechanism by which urethane , a potential hazard in fermented foods, activates the ferroptosis pathway and induces hepatic oxidative damag.

The results provide a theoretical basis and new targets for the mechanism of action of urethane-induced oxidative damage and possible preventive measure.

Ethyl carbamate (EC) is a harmful substance produced during the production and processing of fermented fo.

The International Agency for Research on Cancer (IARC) lists EC as a category 2A carcinog.

Fermented foods such as kimchi, fermented bean curd, rice wine, brandy, e.

are loved by consumers because of their good flavor, and their sales are increasing worldwide, but the risk of EC to human health cannot be ignor.

Existing studies have shown that the liver is one of the important target organs of EC, and its specific toxic effects and mechanism of action are still uncle.

Therefore, in-depth research on the toxicity mechanism of EC is of great significance for the safety prevention and control of EC and improving the safety of fermented foo.

Ferroptosis is a new form of intracellular iron-dependent cell death, which is different from apoptosis and necros.

It is characterized by lipid peroxidation and is associated with some liver pathological stat.

The research team found that EC treatment can cause excessive oxidative stress in liver cells and induce cell death; further studies found that EC treatment significantly increased iron content and lipid peroxidation levels in liver cells and animal livers, resulting in reduced GSH content, GPX4 and Ferritin protein expression levels decreased, and triggered increased levels of inflammation-related factors NLRP3, IL-1β and TNFα and mitochondrial swelling, membrane damage and cristae loss, indicating that EC treatment activated the ferroptosis process in the liv.

Treated with ferroptosis, apoptosis and necrosis inhibitors, it was found that only ferroptosis inhibitor (Fer-1) could effectively restore the protein expression levels of Ferritin and GPX4, increase the content of reduced GSH, and inhibit lipid peroxidation and cytotoxici.

This indicated that ferroptosis was the main cause of EC-triggered liver toxicity; further studies found that EC treatment significantly inhibited the expression levels of key GSH biosynthesis proteins (GCLC and SLC7A11), indicating that EC triggers ferroptosis by inhibiting GSH synthes.

Nrf2 is one of the main transcription factors of cellular antioxidant response and an important regulator of ferroptos.

Nrf2 protein activation can enhance GSH synthesis by up-regulating the expressions of SLC7A11 and GC.

The study found that EC can reduce the activity of the key regulator of ferroptosis Nrf2, inhibit Nrf2 phosphorylation modification and expression in the nucleus and cytoplasm, and reduce the downstream HO-1 and NQO1 protein content, while Nrf2 agonist treatment alleviated EC-induced liver toxici.

These results indicated that EC activated hepatic ferroptosis by inhibiting Nrf2 transcriptional activity and blocking the GSH synthesis pathw.

The above research results provide a theoretical basis and new targets for the mechanism of action and possible prevention and control measures of oxidative damage caused by urethane, a potentially harmful substance in fermented foods, which will help to build an active food safety prevention and control system and ensure that people "on the tip of their tongue.

safet.

Professor Chen Wei is the corresponding author of this article, postdoctoral fellow Xu Yang and doctoral student Li Yuting are the first authors of this artic.

This research was supported by the Zhejiang Provincial Science Fund for Distinguished Young Scholars, the National Natural Science Foundation of China and the Postdoctoral Innovative Talents Support Progr.