Comparative studies on the gastrointestinal lesions caused by several nonsteroidal anti-inflammatory agents in rats

Abstract

The gastrointestinal toxicity of a single oral administration of five nonsteroidal anti-inflammatory agents (NSAIDs) to rats was compared, by a method using 51Cr-labeled red blood cells (RBC), and by macroscopic and microscopic examination. From the profile of gastrointestinal bleeding, the NSAIDs could be divided into a group consisting of aspirin (ASA), oxaprozin (OXP) and 2-[4-(3-methyl-2-butenyl)phenyl]propionic acid (TA), which caused only a transient increase in fecal blood loss based on a gastric lesion, and another group including indomethacin (IM) and ibuprofen (IP), which produced a biphasic increase in the blood loss. The initial phase was caused not only by a gastric lesion but also an intestinal lesion, and the secondary phase originated only in the intestinal lesion. The order of potency causing blood loss was IM much greater than IP greater than ASA much greater than TA greater than OXP. The safety ratio of OXP and TA was shown to be more favorable than that of the other three drugs.

Recombinant Human Epidermal Growth Factor Alleviates Gastric Antral Ulcer Induced by Naproxen: A Non-steroidal Anti Inflammatory Drug

“…This has been manifested with denudation of mucosal glands and inflammatory exudates seen in Group II, Group III and Group V animals. Naproxen is a non-corticosteroid drug with anti-inflammatory and antipyretic effects causing erosions, antral ulceration and petechial bleeding in the mucosa of stomach [5, 6]. It has been demonstrated that the production of oxygen free radicals and lipid peroxidation plays a crucial role in the development of the gastric antral ulcers induced by NSAIDs [7, 8].…”

“…Naproxen is a non-corticosteroid drug with anti-inflammatory, antipyretic and pain relieving properties used more frequently than other NSAIDs for arthritic patients [5, 6]. However, the major cause of concern with the long term use of naproxen is the development of the gastric antral ulcers [7, 8].…”

Effect of naproxen on the hamster gastric antrum: ulceration, adaptation and efficacy of anti‐ulcer drugs

“…This criterion eliminates the fasted rat NSAID models, which produce mainly gastric corpus damage. Damage in these models also tends to be mostly in the form of erosions, rather than ulcers 1 –4 …”

“…Many NSAIDs (non‐steroidal anti‐inflammatory drugs) cause gastric damage in rats 1 –4 . However, NSAIDs are often administered to fasted rats, which results in erosions to the corpus region of the stomach.…”

Digestive System

“…302 Comparative single oral dose studies of several non-steroidal anti-inflammatory agents at three different dose levels in the rat using histology evaluation and measurement of fecal blood loss with 51 Cr-labeled blood cells have also shown that different patterns of ulceration can be produced by different agents when administered under identical conditions. 303 Single oral doses of some non-steroidal anti-inflammatory drugs including aspirin produced widespread superficial damage and desquamation of gastric epithelium with little or no inflammation at six hours following dosing which completely healed two weeks later. This damage was associated with transient fecal blood loss.…”