A new recombinant MS-superoxide dismutase alleviates 5-fluorouracil-induced intestinal mucositis in mice  

作　　者：Xiao-xia Yan Hai-long Li Yi-ting Zhang Shou-yan Wu Heng-lei Lu Xiao-lu Yu Fan-guo Meng Jian-hua Sun Li-kun Gong 

机构地区：[1]Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [2]University of Chinese Academy of Sciences,Beijing 100049,China [3]institute of Molecular Enzymology,Medical College of Soochow University,Suzhou 215123,China [4]Red ox Medical Center for Public Health,Soochow University,Suzhou 215123,China

出　　处：《Acta Pharmacologica Sinica》2020年第3期348-357,共10页中国药理学报（英文版）

基　　金：This study was supported by the National New Drug Creation Program of China(2015ZX09501007-001 to Jian-hua Sun and 2018ZX09201017-004 to Li-kun Gong);the“Strategic Priority Research Program”of the Chinese Academy of Sciences(XDA12050305 to Li-kun Gong).

摘　　要：Intestinal mucositis is a common side effect of anticancer regimens that exerts a negative impact on chemotherapy.Superoxide dismutase(SOD)is a potential therapy for mucositis but efficient product is not available because the enzyme is degraded following oral administration or induces an immune reaction after intravascular infusion.Multi-modified Stable Anti-Oxidant Enzymes?(MS-AOE?)is a new recombinant SOD with better resistance to pepsin and trypsin.We referred it as MS-SOD to distinguish from other SODs.In this study we investigated its potential to alleviate 5-FU-induced intestinal injury and the mechanisms.An intestinal mucositis model was established in C57/BL6 mice by 5-day administration of 5-FU(50 mg/kg every day,ip).MS-SOD(800 IU/10 g,ig)was given once daily for 9 days.5-FU caused severe mucositis with intestinal morphological damage,bodyweight loss and diarrhea;MS-SOD significantly decreased the severity.5-FU markedly increased reactive oxygen species(ROS)and inflammatory cytokines in the intestine which were ameliorated by MS-SOD.Furthermore,MS-SOD modified intestinal microbes,particularly reduced Verrucomicrobia,compared with the 5-FU group.In Caco2 cells,MS-SOD(250–1000 U/mL)dose-dependently decreased tBHP-induced ROS generation.In RAW264.7 cells,MS-SOD(500 U/mL)had no effect on LPS-induced inflammatory cytokines,but inhibited iNOS expression.These results demonstrate that MS-SOD can scavenge ROS at the initial stage of injury,thus play an indirect role in anti-inflammatory and barrier protein protection.In conclusion,MS-SOD attenuates 5-FU-induced intestinal mucositis by suppressing oxidative stress and inflammation,and influencing microbes.MS-SOD may exert beneficial effect in prevention of intestinal mucositis during chemotherapy in clinic.

关 键 词：manganese superoxide DISMUTASE 5-FLUOROURACIL chemotherapy INTESTINAL MUCOSITIS DIARRHEA oxidative stress cytokines INTESTINAL microbes 

分 类 号：R285.5[医药卫生—中药学]