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Int Immunopharmacol. 2018 Dec;65:159-173. doi: 10.1016/j.intimp.2018.10.006. Epub 2018 Oct 10.

Ketotifen fumarate attenuates feline gingivitis related with gingival microenvironment modulation.

Author information

1
Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, Beijing 100193, People's Republic of China.
2
Meilianzhonghe Animal Hospital, Beijing 100077, People's Republic of China.
3
College of Animal Husbandry and Veterinary Medicine, Xinyang Agriculture and Forestry University, Xinyang 464001, People's Republic of China.
4
Animal Hospital, Shanghai Wild Animal Park, Shanghai 200120, People's Republic of China.
5
Luoyang Animal Husbandry Station, Luoyang 471002, People's Republic of China.
6
Yichongtang Animal Hospital, Zhengzhou 450016, People's Republic of China.
7
Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, Beijing 100193, People's Republic of China. Electronic address: xinghui_zhao@163.com.
8
Beijing Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, Beijing 100193, People's Republic of China. Electronic address: zhanzhongzhao@hotmail.com.

Abstract

Gingivitis is evidenced by inflammation of the free gingiva, and still reversible. If left untreated, it may then progress to periodontitis. In the present study, the therapeutical effect of ketotifen fumarate on gingivitis was explored. Domestic cats with varying degrees of gingivitis naturally were enrolled in this study. Subgroups of animals were treated twice daily for one week with or without ketotifen fumarate (5 mg/kg). Effects of ketotifen fumarate were measured on gingival index, cells accumulation, mediators release, receptor-ligand interaction, oxidative stress, MAPK and NF-κB pathways, epithelial barrier and apoptosis. Ketotifen fumarate attenuated the initiation and progression of gingivitis, inhibited the infiltrations of mast cells, B lymphocytes, T lymphocytes, macrophages, neutrophils and eosinophils as well as the release of IgE, β-hexosaminidase, tryptase, chymase, TNF-α, IL-4, and IL-13, influenced endothelial cells, fibroblasts and epithelial cells proliferation and apoptosis, and induced Th2 cells polarization, where ketotifen fumarate also might affect their interactions. Ketotifen fumarate reduced the oxidative stress, and inhibited NF-κB and p38 MAPK related with mast cells and macrophages accumulation. Ketotifen fumarate improved the aberrant expression of ZO-1 and inhibits the following apoptosis. On the other hand, these cells and mediators augmented functional attributes of them involving SCF/c-Kit, α4β7/VCAM-1 and IL-8/IL-8RB interactions, thus creating a positive feedback loop to perpetuate gingivitis, where an inflammation microenvironment was modeled. Our results showed a previously unexplored therapeutic potential of ketotifen fumarate for gingivitis and further suggest that, in addition to biofilms, targeting inflammation microenvironment could be new strategy for the treatment of gingivitis/periodontitis.

KEYWORDS:

Gingival microenvironment; Gingivitis; Ketotifen fumarate; Macrophages; Mast cells

PMID:
30316074
DOI:
10.1016/j.intimp.2018.10.006
[Indexed for MEDLINE]

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