TY - JOUR
T1 - Adhesive Ergothioneine Hyaluronate Gel Protects against Radiation Gastroenteritis by Alleviating Apoptosis, Inflammation, and Gut Microbiota Dysbiosis
AU - Liu, Yaping
AU - Wang, Chengyan
AU - Liu, Ruixue
AU - Zhao, Maoru
AU - Ding, Xuefeng
AU - Zhang, Tingjun
AU - He, Rendong
AU - Zhu, Shuang
AU - Dong, Xinghua
AU - Xie, Jiani
AU - Gu, Zhanjun
AU - Zhao, Yuliang
N1 - Funding Information:
This work is supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDB36000000), National Key R&D Program of China (Nos. 2021YFA1201200 and 2020YFA0710702), National Natural Science Foundation of China (52003031 and 52103337), Directional Institutionalized Scientific Research Platform that relies on the Beijing Synchrotron Radiation Facility of the Chinese Academy of Sciences, and Beijing Natural Science Foundation (No. 2222087).
Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/4/26
Y1 - 2023/4/26
N2 - Radiation gastroenteritis represents one of the most prevalent and hazardous complications of abdominopelvic radiotherapy, which not only severely reduces patients’ life quality but also restricts radiotherapy efficacy. However, there is currently no clinically available oral radioprotector for this threatening disease due to its complex pathogenesis and the harsh gastrointestinal environment. To this end, this study developed a facile but effective oral radioprotector, ergothioneine hyaluronate (EGT@HA) gel, protecting against radiation gastroenteritis by synergistically regulating oxidative stress, inflammation, and gut microbiota. In vitro and cellular experiments verified the chemical stability and free radical scavenging ability of EGT and its favorable cellular radioprotective efficacy by inhibiting intracellular reactive oxidative species (ROS) generation, DNA damage, mitochondrial damage, and apoptosis. At the in vivo level, EGT@HA with prolonged gastrointestinal residence mitigated radiation-induced gastrointestinal tissue injury, apoptosis, neutrophil infiltration, and gut flora dysbiosis. For the first time, this work investigated the protective effects of EGT@HA gel on radiation gastroenteritis, which not only hastens the advancement of the novel gastrointestinal radioprotector but also provides a valuable gastrointestinal radioprotection paradigm by synergistically modulating oxidative stress, inflammation, and gut microbiota disturbance.
AB - Radiation gastroenteritis represents one of the most prevalent and hazardous complications of abdominopelvic radiotherapy, which not only severely reduces patients’ life quality but also restricts radiotherapy efficacy. However, there is currently no clinically available oral radioprotector for this threatening disease due to its complex pathogenesis and the harsh gastrointestinal environment. To this end, this study developed a facile but effective oral radioprotector, ergothioneine hyaluronate (EGT@HA) gel, protecting against radiation gastroenteritis by synergistically regulating oxidative stress, inflammation, and gut microbiota. In vitro and cellular experiments verified the chemical stability and free radical scavenging ability of EGT and its favorable cellular radioprotective efficacy by inhibiting intracellular reactive oxidative species (ROS) generation, DNA damage, mitochondrial damage, and apoptosis. At the in vivo level, EGT@HA with prolonged gastrointestinal residence mitigated radiation-induced gastrointestinal tissue injury, apoptosis, neutrophil infiltration, and gut flora dysbiosis. For the first time, this work investigated the protective effects of EGT@HA gel on radiation gastroenteritis, which not only hastens the advancement of the novel gastrointestinal radioprotector but also provides a valuable gastrointestinal radioprotection paradigm by synergistically modulating oxidative stress, inflammation, and gut microbiota disturbance.
KW - bioadhesive gel
KW - ergothioneine
KW - gastrointestinal radioprotection
KW - gut microbiota
KW - hyaluronate
KW - radiation gastroenteritis
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U2 - 10.1021/acsami.2c23142
DO - 10.1021/acsami.2c23142
M3 - Article
C2 - 37052616
AN - SCOPUS:85154072471
SN - 1944-8244
VL - 15
SP - 19833
EP - 19846
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 16
ER -