? The team of Xinyu Zhang in the School of Public Health of Biomolecules found that bilirubin is degraded by neutrophils...

Bilirubin, the end product of heme degradation, is a strong physiological antioxidant that significantly reduces the risk of
many diseases such as cardiovascular disease, diabetes, and cancer.
Bilirubin can be oxidized and degraded by reactive oxygen species, producing a variety of products, some of which may be involved in the course of
certain diseases.
However, the physiological mechanism of oxidative degradation of bilirubin is currently unclear
.

Recently, the team of Zhang Xinyu of the School of Public Health of Shanghai Jiao Tong University, together with the team of Shangwei Hou of the Joint Research Center for Tumor Immunotherapy of Shanghai Jiao Tong University and the team of Wang Wu of the School of Environmental and Chemical Engineering of Shanghai University, published a paper entitled "A new product of bilirubin degradation by_H2O2" in Biomolecules and its formation in activated neutrophils and in an inflammatory mouse model", found that bilirubin is oxidized and degraded by_H2O2to produce hematinic acid and another new product, named_BHP2
。 These two products were detectable in mouse neutrophils incubated with bilirubin at fairly high concentrations, indicating that neutrophils were effective in degrading bilirubin
.
The use of H2O2-specific fluorescent probes demonstrated high concentrations of H2O2 in bilirubin-incubated neutrophils, suggesting that the degradation of bilirubin by neutrophils may be mediated by_H2O2.

Neutrophils are a key cell involved in the inflammatory response, and when inflammation occurs, a large number of neutrophils gather and activate at the site of inflammation, so bilirubin degradation can be expected to occur at the site
of inflammation.
To this end, the authors established a mouse model of subcutaneous inflammation accompanied by bleeding, and found that the content of heme acid and BHP2 in the skin of the inflamed/bleeding site reached 6 times and 36 times that of normal skin, respectively, validating the above hypothesis
.

To investigate the physiological activity of the degradation products, the authors examined the neurotoxicity of both products using an animal model of nematodes, and the results showed significant neurotoxicity at 100 nM for BHP2 and no neurotoxicity
for heme acid.

Bilirubin is an endogenous compound that is constant in the body, so the findings suggest that bilirubin degradation by neutrophils may be a pathophysiological process that is ubiquitous in inflammatory situations, and the degradation products may be used as inflammatory markers and may also be involved in disease processes
.

Feifei Yu, a master's student at the School of Environmental and Chemical Engineering of Shanghai University, and Dr.
Yao Yuan from the Joint Research Center for Tumor Immunotherapy of Shanghai Jiao Tong University-Hangzhou Future Science and Technology City are co-first authors of the paper, Xinyu Zhang, a researcher at the School of Public Health of Shanghai Jiao Tong University, Shangwei Hou from the Joint Research Center for Tumor Immunotherapy of Shanghai Jiao Tong University-Hangzhou Future Science and Technology City, and Wu Wang, a researcher at the School of Environmental and Chemical Engineering of Shanghai University, are co-corresponding authors
.
This research work was supported
by the National Natural Science Foundation of China.