1. A new recombinant MS-superoxide dismutase alleviates 5-fluorouracil-induced intestinal mucositis in mice
- Author
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Likun Gong, Fan-guo Meng, Xiao-xia Yan, Hai-long Li, Henglei Lu, Xiao-lu Yu, Shou-yan Wu, Yi-ting Zhang, and Jianhua Sun
- Subjects
Male ,0301 basic medicine ,Side effect ,diarrhea ,Administration, Oral ,Inflammation ,Pharmacology ,chemotherapy ,medicine.disease_cause ,Article ,manganese superoxide dismutase ,Proinflammatory cytokine ,Superoxide dismutase ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Oral administration ,Mucositis ,medicine ,Animals ,oxidative stress ,5-fluorouracil ,Pharmacology (medical) ,Intestinal Mucosa ,intestinal microbes ,chemistry.chemical_classification ,Reactive oxygen species ,biology ,Superoxide Dismutase ,business.industry ,General Medicine ,intestinal mucositis ,medicine.disease ,Recombinant Proteins ,cytokines ,Mice, Inbred C57BL ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Fluorouracil ,medicine.symptom ,business ,Injections, Intraperitoneal ,Oxidative stress - Abstract
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.
- Published
- 2019