文献类型：期刊文献

英文题名：Irinotecan cause the side effects on development and adult physiology, and induces intestinal damage via innate immune response and oxidative damage in Drosophila

作者：He, Jianzheng[1,2,3,4];Han, Shuzhen[1,2];Wang, Yixuan[5];Kang, Qian[1,2];Wang, Xiaoqian[1,2];Su, Yun[1,2,4];Li, Yaling[1,2,3,4];Liu, Yongqi[1,4];Cai, Hui[3,6];Xiu, Minghui[4,5]

第一作者：He, Jianzheng;何建政;和建政

通信作者：Cai, H[1];Liu, YQ[2];Xiu, MH[2]

机构：[1]Gansu Univ Chinese Med, Tradit Chinese Med Res Gansu Coll & Univ, Prov level Key Lab Mol Med Major Dis & Prevent & T, Lanzhou 730000, Peoples R China;[2]Gansu Univ Chinese Med, Coll Basic Med, Lanzhou 730000, Peoples R China;[3]Gansu Prov Hosp, NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou 730000, Peoples R China;[4]Gansu Univ Chinese Med, Key Lab Transfer Dunhuang Med Prov & Ministerial L, Lanzhou 730000, Peoples R China;[5]Gansu Univ Chinese Med, Coll Publ Hlth, Lanzhou 730000, Peoples R China;[6]Gansu Prov Hosp, Key Lab Mol Diagnost & Precis Med Surg Oncol Gansu, Lanzhou 730000, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Prov Hosp, NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou 730000, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Key Lab Transfer Dunhuang Med Prov & Ministerial L, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2023

卷号：169

外文期刊名：BIOMEDICINE & PHARMACOTHERAPY

收录：;Scopus(收录号：2-s2.0-85177073687);WOS:【SCI-EXPANDED(收录号:WOS:001119816300001)】；

基金：This work was supported by the Gansu Natural Science Foundation (No. 23JRRA1202) , Postdoctoral Research Foundation of China (No.2023MD734146) , Foundation from NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor (No. NHCDP2022006) , Long-yuan Youth Innovation and Entrepreneurship Talent Project. Gansu Province Excellent Doctoral Fundation (No. 23JRRA1224) .r 2023MD734146) , Foundation from NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor (No. NHCDP2022006) , Long-yuan Youth Innovation and Entrepreneurship Talent Project. Gansu Province Excellent Doctoral Fundation (No. 23JRRA1224) .

语种：英文

外文关键词：Chemotherapy; Irinotecan; Side effects; Drosophila melanogaster; Intestine

摘要：Chemotherapy leads to significant side effects in patients, especially in the gut, resulting in various clinical manifestations and enhanced economic pressure. Until now, many of the underlying mechanisms remain poorly understood. Here, we used Drosophila melanogaster (fruit fly) as in vivo model to delineate the side effects and underlying mechanisms of Irinotecan (CPT-11). The results showed that administration of CPT-11 delayed larval development, induced imbalance of male to female ratio in offspring, shortened lifespan, impaired locomotor ability, changed metabolic capacity, induced ovarian atrophy, and increased excretion. Further, CPT-11 sup-plementation dramatically caused intestinal damages, including decreased intestinal length, increased crop size, disrupted gastrointestinal acid-based homeostasis, induced epithelial cell death, and damaged the ultrastructure and mitochondria structure of epithelial cells. The cross-comparative analysis between transcriptome and bio-information results showed that CPT-11 induced intestinal damage mainly via regulating the Toll-like receptor signaling, NF-kappa B signaling, MAPK signaling, FoxO signaling, and PI3K-AKT signaling pathways. In addition, CPT-11 led to the intestinal damage by increasing ROS accumulation. These observations raise the prospects of using Drosophila as a model for the rapid and systemic evaluation of chemotherapy-induced side effects and high-throughput screening of the protective drugs.