Time course of mucosal cell proliferation following acute aspirin injury in rat stomach

Abstract

The time course of replicating cell proliferation in the gastric fundic mucosa following acute aspirin-induced injury was determined by BrdU labeling. Gastric erosions were produced in adult rats by gastric gavage using aspirin (200 mg/kg) suspended in 0.15 M HCl. Lesion scores indicated significant gross injury in the aspirin-treated rats at all times measured (from 2 to 48 hr). BrdU labeling was not elevated at 2 or 8 hr after gavage. A significant increase in labeling was observed at 15 hr, reached a maximum at 16 hr, and declined with a slight, but significant increase still present at 48 hr. Elevations in BrdU labeling were uniform and seen in areas adjacent to and distant from the gross injury. The BrdU labeling in the fasted control rats decreased during this same time period. The height of the proliferative zone was not altered from control in the aspirin-treated rats despite the marked differences in proliferation activity. This study demonstrates the importance of the time course in the assessment of mucosal cell proliferation following injury.

Age-Related Changes in Gastric Mucosal Repair and Proliferative Activities in Rats Exposed Acutely to Aspirin

“…In the present study, we have failed to observe the increases in proliferative activities and expression of TGF-· reported by other investigators [5,12]. The reason for this discrepancy may be related to two major differences in methodology between our present study and previous reports [5,12]. These include: (1) the method and timing of assessing cell proliferation, and (2) the method of injury induction (i.e.…”

“…TGF-·, a peptide related to epidermal growth factor, with which it shares identical gastric epithelial receptors, is generally expressed by the gastric mucosa in increased amounts after acute gastric mucosal injury induced by acidified taurocholate [12] and has been postulated to play a role in mucosal repair [12]. In the present study, we have failed to observe the increases in proliferative activities and expression of TGF-· reported by other investigators [5,12]. The reason for this discrepancy may be related to two major differences in methodology between our present study and previous reports [5,12].…”

“…In the present study, we have also attempted to correlate the mucosal regneration process with gastric mucosal proliferative activities because (1) gastric mucosal proliferation is thought to be an integral component of mucosal defense and healing [2,5], and (2) age-related changes in gastric mucosal proliferation may represent a potential explanation for the delay in the repair of gastric mucosal injury observed in the aged rats. We chose to assess two proliferative markers, namely PCNA and TGF-·.…”

“…injurious agent and dosage). In most studies showing increases in mucosal proliferative activities, epithelial cell proliferation was assessed by 5-bromo-2)-deoxyuridine (BrdU) immunohistochemistry [5,13], whereas we chose to assess PCNA and TGF-· immunoreactivities. Recently, Ohning and Guth [5] using the BrdU labeling method, have shown that the major increase in gastric mucosal proliferation occurred between 15 and 17 h after injury induced by ASA at 200 mg/kg, whereas we chose to assess proliferative activities at 3 and 24 h after a smaller dose of ASA (i.e.…”

“…Because there is little information on the influence of aging on gastric mucosal repair after acute exposure to ASA or NSAIDs in humans or animals, we have designed the present study to determine whether there are any age-related changes in the repair of acute gastric mucosal injury induced by ASA in Fischer 344 rats. Moreover, we have examined the influence of aging on gastric mucosal proliferative activities [2,5], a major component of gastric mucosal defense and repair mechanisms [2,5], in the present study.…”