Suppression of neutrophil extracellular traps is responsible for the amelioration of chemotherapeutic intestinal injury by the natural compound PEITC

Intestinal injury is one of the most debilitating side effects of many chemotherapeutic agents, such as irinotecan hydrochloride (CPT-11). Accumulating evidence indicates that neutrophil extracellular traps (NETs) play a critical role in the symptoms of ischemia and inflammation related to chemother...

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Published in:Toxicology and applied pharmacology 2024-03, Vol.484, p.116857-116857, Article 116857
Main Authors: Bai, Mei, Li, Shuaifei, Zhang, Cui, An, Ning, Wang, Jie, Qin, Jia, Jia, Rumeng, Liu, Wentao, Cheng, Jingcai, Wu, Xuefeng, Xu, Qiang
Format: Article
Language:English
Subjects:
Animals
Chemotherapeutic intestinal injury
Extracellular Traps
Intestinal Diseases
Irinotecan
Ischemia
Isothiocyanates - pharmacology
Mice
NETs inhibition
Neutrophil
Phenethyl isothiocyanate
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Summary:Intestinal injury is one of the most debilitating side effects of many chemotherapeutic agents, such as irinotecan hydrochloride (CPT-11). Accumulating evidence indicates that neutrophil extracellular traps (NETs) play a critical role in the symptoms of ischemia and inflammation related to chemotherapy. The present study investigated the effects and possible mechanisms of phenethyl isothiocyanate (PEITC) in inhibiting NETs and alleviating chemotherapeutic intestinal injury. CPT-11 induced robust neutrophil activation, as evidenced by increased NETs release, intestinal ischemia, and mRNA expression of inflammatory factors. PEITC prolonged the clotting time of chemotherapeutic mice, improved the intestinal microcirculation, inhibited the expression of inflammatory factors, and protected the tight junctions of the intestinal epithelium. Both in vivo and in vitro experiments revealed that PEITC directly suppresses CPT-11-induced NETs damage to intestinal cells, resulting in significant attenuation of epithelial injury. These results suggest that PEITC may be a novel agent to relieve chemotherapeutic intestinal injury via inhibition of NETs. [Display omitted] •PEITC, a natural isothiocyanate, ameliorated chemotherapy-induced enterocolitis.•PEITC exerts protective effects of intestinal epithelium via the inhibition of NETs.•NETs may be an important target for the treatment of chemotherapeutic injury.
ISSN:0041-008X
1096-0333
DOI:10.1016/j.taap.2024.116857