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Rodent Model of Diffuse Acute and Chronic Gastritis with Translational Relevance
Author(s) -
Csekő Kata,
Deng Xiaoming,
Pécsi Dániel,
Hegedűs Ivett,
Perkecz Anikó,
Szabó Imre,
Helyes Zsuzsanna,
Szabó Sándor
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1001.4
Subject(s) - trpv1 , edema , infiltration (hvac) , inflammation , medicine , gastritis , glutathione , pathology , endocrinology , chemistry , gastroenterology , transient receptor potential channel , stomach , receptor , biochemistry , enzyme , physics , thermodynamics
Objective Stress & anti‐inflammatory drugs induce focal superficial erosions or ulcers, however, there has been no animal model of diffuse gastritis. Sulfhydryl (SH) groups offer gastroprotection, therefore we postulated that drinking water containing SH alkylators may cause diffuse lesions in rats by depleting glutathione (GSH). Transient Receptor Potential Vanilloid 1 (TRPV1) & Ankyrin 1 (TRPA1) ion channels play role in inflammation, but their functions in gastritis have not been investigated. After demonstrating decreased TRPV1 expression in human chronic gastritis biopsies of, we wanted to optimalize and characterize a translational animal model to gain insight into the molecular mechanisms of gastritis. Aims 1) Test the gastritis‐inducing effect of the SH alkylator iodoacetamide (IA); 2)observe potential strain differences in the inflammatory reactions; 3)investigate TRPV1/A1 expression alterations in comparison with human samples. Methods We administered 0.05% & 0.2% IA to the drinking water of Wistar & CFY male rats (8–12‐week‐old) for 7 & 14days. Body weight & water consumption were recorded daily. Macroscopic lesions were scored by the extent of hyperemia, erosions/ulcers & sections were taken for histological assessment. TRPV1/A1 mRNA expressions were determined by qPCR. Results IA intake resulted in concentration‐dependent weight loss & reduced water consumption. Diffuse hyperemia & erosions were observed macroscopically after 7 days in all IA‐exposed rats & in 14 days ulcers were induced by both concentrations. Microscopically submucosal edema was observeable followed by leukocytic & lymphocytic infiltration. Susequently, superficial, often hemorrhagic mucosal erosions were seen after 7 days, followed by ulcers in 14 days. In CFY rats, TRPV1 & TRPA1 mRNA expressions were significantly lower in the antrum, similarly to human biopsies. In Wistar rats TRPV1 expression did not change, but a markedTRPA1 increase was seen in both time intervals. Conclusions 1) IA ingestion for 7 & 14 days caused diffuse acute & chronic gastritis, associated with hemorrhagic erosions & ulcers. 2) Ion channel expression showed a strain difference; TRPA1 mRNA level increased in Wistar rats with both IA‐concentrations & at both time intervals. 3) Since TRPV1/A1 expression in CFY rats was similar to the human gastritis, this strain has translational value to investigate the pathophysiological role of these channels in chronic gastritis. Support or Funding Information University funds and grant from Hungary Academy of Science.