Intrarectally administered polaprezinc attenuates the development of dextran sodium sulfate‑induced ulcerative colitis in mice

Liu,Zhaoyang; Xie,Wenbo; Li,Mingru; Liu,Jing; Liang,Xiao; Li,Tao

doi:10.3892/etm.2019.8155

Intrarectally administered polaprezinc attenuates the development of dextran sodium sulfate‑induced ulcerative colitis in mice

Authors:
- Zhaoyang Liu
- Wenbo Xie
- Mingru Li
- Jing Liu
- Xiao Liang
- Tao Li
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Affiliations: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China, Jilin Province Broadwell Pharmaceutical Co., Ltd., Liaoyuan, Jilin 130000, P.R. China, Institute of Basic Medical Sciences of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, P.R. China
Published online on: October 31, 2019 https://doi.org/10.3892/etm.2019.8155
Pages: 4927-4934

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Abstract

Polaprezinc (PZ), a chelate of zinc and L‑carnosine, has been widely used in the treatment of gastric ulcers since 1994. In recent years, researchers have found PZ to have a beneficial effect on various experimentally induced models of colitis in mice. In the present study, 6% dextran sodium sulfate (DSS) was used to induce a model of ulcerative colitis (UC) in Institute of Cancer Research mice. The therapeutic effect and mechanism of PZ action in a model of UC was studied in order to provide an experimental basis for the clinical application of PZ in UC treatment. The effect of PZ on UC was evaluated in five groups of mice: A vehicle control only group, a DSS model control group (DSS, 6%), a validated treatment control group (DSS 6% + Mesalamine), a low‑dose PZ treatment group (DSS 6% + PZ 60 mg/kg) and a high‑dose PZ group (DSS 6% + PZ 120 mg/kg). After the animals were sacrificed, blood was collected and the serum levels of NF‑κB and tumor necrosis factor‑α (TNF‑α) were measured. Changes in histology were observed by light microscopy. The protein levels of AKT, phosphorylated AKT and heat shock protein 70 (HSP70) were determined by western blot analysis. The results suggested that PZ reduced the DSS‑induced increase in the inflammatory proteins TNF‑α and NF‑κB in the UC model. The high‑dose of PZ also increased the HSP70 protein level, inhibited AKT phosphorylation in a DSS‑induced UC animal model, and decreased white blood cell and neutrophil % counts compared to levels in an untreated DSS control group. Histopathology indicated that the mice of the DSS model group had irregular colonic villi, a large number of inflammatory cells and mucosal damage, whereas mice of the group treated with PZ had small intestinal villus morphology and their villi showed signs of recovery from the damage of UC. The results of the present study indicated that PZ significantly alleviates DSS‑induced UC in mice, relieves diarrhea, and inhibits the phosphorylation of inflammatory factors and the inflammatory AKT signaling pathway.

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