anewrecombinantmssuperoxidedismutasealleviates5fluorouracilinducedintestinalmucositisinmice

doi:10.1038/s41401-019-0295-8

	anewrecombinantmssuperoxidedismutasealleviates5fluorouracilinducedintestinalmucositisinmice
	Yan Xiaoxia 1; Li Hailong 2; Zhang Yiting 1; Wu Shouyan 1; Lu Henglei 1; Yu Xiaolu 1; Meng Fanguo 2; Sun Jianhua 1; Gong Likun 1
刊名	actapharmacologicasinica
	2020
卷号	41 期号:3 页码:348
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
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? (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 Caco_2 cells, MS-SOD (250–1000 U/mL) dosedependently 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.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280766]
专题	中国科学院上海药物研究所
作者单位	1.中国科学院上海药物研究所 2.苏州大学
推荐引用方式 GB/T 7714	Yan Xiaoxia,Li Hailong,Zhang Yiting,et al. anewrecombinantmssuperoxidedismutasealleviates5fluorouracilinducedintestinalmucositisinmice[J]. actapharmacologicasinica,2020,41(3):348.
APA	Yan Xiaoxia.,Li Hailong.,Zhang Yiting.,Wu Shouyan.,Lu Henglei.,...&Gong Likun.(2020).anewrecombinantmssuperoxidedismutasealleviates5fluorouracilinducedintestinalmucositisinmice.actapharmacologicasinica,41(3),348.
MLA	Yan Xiaoxia,et al."anewrecombinantmssuperoxidedismutasealleviates5fluorouracilinducedintestinalmucositisinmice".actapharmacologicasinica 41.3(2020):348.