Early histological features of small intestinal injury induced by indomethacin

Abstract

SUMMARY The early histological features of indomethacin‐induced jejunal injury in the rat are described in tissues preserved by perfusion‐fixation with 10% formolsaline. After an oral dose of indomethacin (15 mg/kg, known to cause severe multifocal ulceration of the rat jejunum), groups of rats were anaesthetized with subsequent perfusion‐fixation of the gastrointestinal tract at 1, 2, 3, 6 and 48 h after dosing. Using routine light microscopic techniques, we have observed a sequence of four distinct stages, in time, of small intestinal injury. The earliest histological features were shortening of the villi, epithelial stratification, basal lamina degeneration, eosinophil degranulation and infiltration of the epithelium prior to infiltration of the mucosa by neutrophils. We consider that these earliest changes, seen at 1, 2 and 3 h, represent a distinct histological entity termed Type 1 change or villous ‘tufting’. Type 2 change includes all of the features of Type 1 change plus the subsequent infiltration of the mucosa by neutrophils at 2, 3 and 6 h. Type 3 change includes necrosis of the upper‐third of the villi and was mainly seen at 3 and 6 h. Type 4 change describes extreme injury to more than one‐third of the mucosa with severe, acute inflammation and perforation of the bowel wall by 48 h. Although a small number of neutrophils had appeared to infiltrate the mucosa as early as 2 h after dosing, they were only significantly increased at 3, 6 and 48 h. Possible pathogenic mechanisms involved in shortening of villi as a result of smooth muscle contraction and the role of mucosal eosinophils in NSAID‐induced jejunal injury in the rat are discussed.

NSAID-Induced Enteropathy: Are the Currently Available Selective COX-2 Inhibitors All the Same?

“…The histologic evaluation of intestinal injury was carried out as previously described by Anthony et al (1993). Upon removal, the whole intestinal tract was immediately injected with 10% formalin and left in the same fixative solution.…”

“…Histologic damage was assessed by two observers, blind to the treatment, according to the score system proposed by Anthony et al (1993) with minor changes. The intestinal damage was classified as reported in Table 1.…”

New Therapeutic Strategy for Amino Acid Medicine: Prophylactic and Healing Promoting Effect of Monosodium Glutamate Against NSAID-Induced Enteropathy

“…Since mucus plays a crucial part in the innate host defense against intestinal pathogens and irritants, it is possible that the enhanced intestinal contraction plays a role in the pathogenesis of NSAID-induced intestinal damage by accelerating bacterial invasion in the mucosa. Alternatively, intestinal hypermotility causes mucosal hypoxia and microvascular injury due to smooth muscle contraction, leading to neutrophil infiltration and the release of various cytokines (35). Anyhow, these functional alterations weaken the intestinal barrier, resulting in bacterial invasion, which in turn increases iNOS expression and NO production, eventually resulting in NSAID-induced intestinal damage (21,22).…”

Phytochemical screening and antiulcerogenic effect of <i> Moringa oleifera</i> aqueous leaf extract

“…The deleterious effect of indomethacin on gastric duodenal mucosa is mainly attributed to direct damage of mucosal cell and its ability to reduce the formation of prostaglandins (Graham et al, 1995). The most common indomethacin induced adverse reaction is associated with the upper gastrointestinal tract and include subjective discomfort, ulcers and bleeding; the incidence of ulceration and bleeding occurs in a dose dependent fashion (Anthony et al, 1993).…”