Oral Administration of Polaprezinc Attenuates Fluorouracil‐induced Intestinal Mucositis in a Mouse Model |
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| Authors: | Zhaoyang Liu Wenbo Xie Mingru Li Nan Teng Xiao Liang Ziqiang Zhang Zhaogang Yang Xiaobing Wang |
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| Affiliation: | 1. Tumor Marker Research Center, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;2. Jilin Province Broadwell Pharmaceutical Co., Ltd., Changchun, China;3. State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;4. NSF Nanoscale Science and Engineering Center (NSEC), The Ohio State University, Columbus, OH, USA |
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| Abstract: | 5‐Fluorouracil (5‐FU) has broadly been applied to treat colorectal cancer as one of the most effective chemotherapeutic agents. However, it frequently causes intestinal mucosal injury and related side effects, such as abdominal pain and diarrhoea, which limit the use of 5‐FU in a clinic setting. Polaprezinc has gradually become known as a mucosal protective agent for the management of gastric ulcer. This study aimed to investigate the prophylactic efficacy of Polaprezinc administered orally against intestinal mucositis induced by 5‐FU in mice on the condition that the antitumour effect could not be compromised. We induced intestinal mucositis in SPF‐grade ICR mice with 5‐FU, and evaluated intestinal damage in the absence or presence of Polaprezinc. We examined the score of diarrhoea and the loss of weight after the 5‐FU treatment and assessed the integrity of villus and the proliferation of small intestine crypt cells by haematoxylin and eosin staining and PCNA immunohistochemical detection. The antitumour effect of 5‐FU on colorectal cancer was assessed with or without Polaprezinc in a xenograft model. The result showed that Polaprezinc significantly reduced the elevated diarrhoea score and the body‐weight loss caused by 5‐FU abolished histological abnormality and crypt cell hypoproliferation in a dose‐dependent manner, without affecting 5‐FU efficacy on colon xenograft tumour in mice. We conclude that Polaprezinc could inhibit 5‐FU‐induced diarrhoea and alleviate the weight loss during 5‐FU chemotherapy, as a possible candidate for treatment and prevention of intestinal mucositis, through protecting intestinal mucosa and improving the quality of life after chemotherapy. |
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