A new recombinant MS-superoxide dismutase alleviates 5-fluorouracil-induced intestinal mucositis in mice
| العنوان: | A new recombinant MS-superoxide dismutase alleviates 5-fluorouracil-induced intestinal mucositis in mice |
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| المؤلفون: | Likun Gong, Fan-guo Meng, Xiao-xia Yan, Hai-long Li, Henglei Lu, Xiao-lu Yu, Shou-yan Wu, Yi-ting Zhang, Jianhua Sun |
| المصدر: | Acta Pharmacologica Sinica |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1745-7254 1671-4083 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ab2fae1399d54e8daf24f9cf8fd901c6Test https://doi.org/10.1038/s41401-019-0295-8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ab2fae1399d54e8daf24f9cf8fd901c6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17457254 16714083 |
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