A new recombinant MS-superoxide dismutase alleviates 5-fluorouracil-induced intestinal mucositis in mice
文献类型：期刊论文
| 作者 | Yan, Xiao-xia1,2; Li, Hai-long3,4; Zhang, Yi-ting1,2; Wu, Shou-yan1,2; Lu, Heng-lei1; Yu, Xiao-lu1,2; Meng, Fan-guo3,4; Sun, Jian-hua1 ; Gong, Li-kun1,2
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 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. |
| WOS关键词 | DIARRHEA ; CELLS ; IMPROVEMENTS ; EXPRESSION ; APOPTOSIS ; OCCLUDIN |
| 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研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000514159600007 |
| 出版者 | NATURE PUBLISHING GROUP |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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