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

doi:10.1038/s41401-019-0295-8

	A new recombinant MS-superoxide dismutase alleviates 5-fluorouracil-induced intestinal mucositis in mice
	Yan, Xiao-xia 1,2; Li, Hai-long 3,4; Zhang, Yi-ting 1,2; Wu, Shou-yan 1,2; Lu, Heng-lei 1; Yu, Xiao-lu 1,2; Meng, Fan-guo 3,4; Sun, Jian-hua 1; Gong, Li-kun 1,2
刊名	ACTA PHARMACOLOGICA SINICA
	2020-03-01
卷号	41 期号:3 页码:348-357
关键词	manganese superoxide dismutase 5-fluorouracil chemotherapy intestinal mucositis diarrhea oxidative stress cytokines intestinal microbes
ISSN号	1671-4083
DOI	10.1038/s41401-019-0295-8
通讯作者	Sun, Jian-hua(jhsun@cdser.simm.ac.cn) ; Gong, Li-kun(lkgong@cdser.simm.ac.cn)
英文摘要	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(R) (MS-AOE(R)) 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.
资助项目	National New Drug Creation Program of China[2015ZX09501007-001] ; National New Drug Creation Program of China[2018ZX09201017-004] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050305]
WOS关键词	DIARRHEA ; CELLS ; IMPROVEMENTS ; EXPRESSION ; APOPTOSIS ; OCCLUDIN
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000514159600007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281517]
专题	中国科学院上海药物研究所
通讯作者	Sun, Jian-hua; Gong, Li-kun
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Soochow Univ, Inst Mol Enzymol, Med Coll, Suzhou 215123, Peoples R China 4.Soochow Univ, Redox Med Ctr Publ Hlth, Suzhou 215123, Peoples R China
推荐引用方式 GB/T 7714	Yan, Xiao-xia,Li, Hai-long,Zhang, Yi-ting,et al. A new recombinant MS-superoxide dismutase alleviates 5-fluorouracil-induced intestinal mucositis in mice[J]. ACTA PHARMACOLOGICA SINICA,2020,41(3):348-357.
APA	Yan, Xiao-xia.,Li, Hai-long.,Zhang, Yi-ting.,Wu, Shou-yan.,Lu, Heng-lei.,...&Gong, Li-kun.(2020).A new recombinant MS-superoxide dismutase alleviates 5-fluorouracil-induced intestinal mucositis in mice.ACTA PHARMACOLOGICA SINICA,41(3),348-357.
MLA	Yan, Xiao-xia,et al."A new recombinant MS-superoxide dismutase alleviates 5-fluorouracil-induced intestinal mucositis in mice".ACTA PHARMACOLOGICA SINICA 41.3(2020):348-357.