KjG The Korean Journal of Gastroenterology Korean J Gastroenterol 1598-9992 2233-6869 Korean Society of Gastroenterology 10.4166/kjg.2014.63.6.341 kjg-63-341 Original Article Difficult Establishment of a Chronic Nonsteroidal Anti-inflammatory Drugs Induced Gastric Inflammation Rat Model due to Gastric Adaptation and Small Bowel Damage LeeByoung Hwan 1 3 KimNayoung 1 4 NamRyoung Hee 1 LeeJu Yup 1 LeeHye Seung 2 LeeChang Hee 3 ParkJi Hyun 4 LeeDong Ho 1 4 Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea Department of Internal Medicine, Incheon Sarang Hospital, Incheon, Korea Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea Correspondence to: Nayoung Kim, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 463-707, Korea. Tel: +82-31-787-7008, Fax: +82-31-787-4051, E-mail: nayoungkim49@empas.com 10 2014 04 10 2014 636 341 347 Copyright © 2014 Korean Ophthalmological Society 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background/Aims

The prevalence of peptic ulcer disease has not decreased mainly due to an increase in the use of NSAIDs. This study was conducted in order to determine whether a chronic NSAID-induced gastric inflammation model could be established by repeated administration of NSAID.

 Methods

Indomethacin (10 mg/kg) was administered once per week for six weeks in 8- and 26-week rats and animals were sacrificed every week after administration. Gross ulcer index, histologic damage index, myeloperoxidase (MPO) activity, and mucus (glucosamine) levels were measured. Small bowel damage was also evaluated.

 Results

Gross gastric damage index showed a peak level at three weeks and then decreased slowly in the 26-week indomethacin group. Gastric mucosal glucosamine level increased in both the 8-week (p=0.038) and 26-week groups (p=0.007). In addition, gastric mucosal MPO level decreased in the 8-week group (p=0.018) but did not show a decrease in the 26-week group. Small bowel damage began to occur at three weeks during the schedule and eight of 36 rats (22.2%) died due to perforation or peritonitis of the small bowel in the 8- and 26-week indomethacin groups, respectively.

 Conclusions

Due to gastric adaptation and small bowel damage, repeated administration of NSAID to experimental animals may not be an adequate method for establishment of the chronic gastric inflammation model.

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Schematic diagram of study design.

Gross gastric damage index during the study period in the 8-week and 26-week indomethacin groups. Data are shown with mean±standard error.

Histological index of gastric mucosal damage during the study period in the 8-week and 26-week indomethacin groups. Data are shown with mean±standard error.

Myeloperoxidase levels in the small bowel during the study period in 8- and 26-week groups. No statistically significant trend was observed. Data are shown with mean±standard error.

Occurrence of Small Bowel Damage in the Indomethacin Group during Six Weeks in 8- or 26-Week Rats

Rats' age (week) Perforation or peritonitis a
1 Week 2 Week 3 Week 4 Week 5 Week 6 Week Total
8 0/6 2/6 2/3 2/3 1/4 0/6 7/28 (25.0%)
16 0/6 0/6 2/5 2/3 0/3 0/5 4/28 (14.3%)

Perforation or peritonitis number/total sacrifice rat number.

Time Trend of Gastric Mucosal Myeloperoxidase (MPO) and Glucosamine Levels in the Indomethacin Groups

  1 Week 2 Week 3 Week 4 Week 5 Week 6 Week p-value a
Indomethacin MPO (ng/mg protein) 0.68±0.19 0.54±0.09 0.64±0.12 0.26±0.03 0.31±0.06 0.22±0.05 0.018
8-week-rat group Glucosamine (mg/g mucosa) 8.36±1.09 8.18±0.59 8.01±1.15 9.31±1.35 9.59±2.10 12.24±0.91 0.038
Indomethacin MPO (ng/mg protein) 0.51±0.07 0.72±0.11 0.71±0.07 0.36±0.06 0.31±0.02 0.48±0.11 0.270
26-week-rat group Glucosamine (mg/g mucosa) 7.74±1.35 6.49±1.70 10.54±1.31 11.19±1.07 11.73±2.53 14.06±1.95 0.007

Data are presented as mean±standard error.

By regression analysis.