Korean J Gastroenterol.  2014 Jun;63(6):341-347. 10.4166/kjg.2014.63.6.341.

Difficult Establishment of a Chronic Nonsteroidal Anti-inflammatory Drugs Induced Gastric Inflammation Rat Model due to Gastric Adaptation and Small Bowel Damage

• Lee BH
• Kim N
• Nam RH
• Lee JY
• Lee HS
• Lee CH
• Park JH
• Lee DH

• KMID: 2234034
• DOI: http://doi.org/10.4166/kjg.2014.63.6.341

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.

Keyword

Adaptation; Glucosamine; Gastric; Nonsteroidal anti-inflammatory agents; Small intestine

MeSH Terms

Animals
Anti-Inflammatory Agents, Non-Steroidal/*toxicity
Disease Models, Animal
Gastric Mucosa/*drug effects/enzymology/pathology
Glucosamine/metabolism
Indomethacin/*toxicity
Intestine, Small/*drug effects/pathology
Male
Peroxidase/metabolism
Rats
Rats, Sprague-Dawley
Time Factors
Anti-Inflammatory Agents, Non-Steroidal
Glucosamine
Indomethacin
Peroxidase

Figure

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  Fig. 1. Schematic diagram of study design.

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  Fig. 2. Gross gastric damage index during the study period in the 8-week and 26-week indomethacin groups. Data are shown with mean±standard error.

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  Fig. 3. 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.

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  Fig. 4. 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.

Reference

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