Paracetamol Confers Resistance to Ethanol-induced Gastric Mucosal Damage in Rats

Abstract

Paracetamol given orally or subcutaneously did not produce any observable gastric mucosal damage, nor did it change the acidity of the residual secretion in rat stomachs. However, it delayed the gastric emptying rate and increased the residual volume of gastric secretion. Pretreatment with paracetamol 250 mg kg-1 significantly prevented ethanol-induced gastric ulceration. Although it did not influence ethanol-stimulated acid secretion, it increased the mucosal mucus content in the ethanol-treated animals. The findings suggest that the protective mechanism of paracetamol against ethanol-induced damage is likely to be due to improved gastric mucosal integrity, through an increase in the adherent mucosal mucus which protects the underlying delicate cellular structures.

Protective Effect of Acetaminophen against Acute Gastric Mucosal Lesions Induced by Ischemia-Reperf usion in the Rat

“…Sev eral mechanisms have been proposed for the protection of gastric mucosa by acetamino phen. For example, in gastric lesions induced by the water immersion restraint stress meth od, acetaminophen was thought to protect the gastric mucosa by inhibiting the reduction in gastric PGE2 levels [4,24] or to stimulate PGEi synthesis in the gastric mucosa [25], However, in some studies, acetaminophen failed to increase PGE2 content but enhanced gastric secretion of mucus or directly pro tected the gastric epithelial cells, independent of PG synthesis [3,6,23]. Thus, gastric pro tection by acetaminophen is not attributable to a single mechanism.…”

“…In con trast to nonsteroidal anti-inflammatory drugs (NSAIDs), a previous study has shown that acetaminophen does not induce serious gastrointestinal damage in man [1], In addition, administration of a high dose of acetamino phen (orally or intraperitoneally) has been reported to exhibit a protective effect on gas tric mucosa against various irritants, such as NSAIDs, ethanol and stress [2][3][4], It has been stated that acetaminophen may stimulate prostaglandin Ea (PGE2) synthesis to protect gastric mucosa [5], On the contrary, some reports have suggested that protection by acetaminophen was not attributable to the stimulation of PG synthesis but due to an increase in mucus secretion [3] or to a direct effect on gastric mucosal cells [6], Other studies have reported acetamino phen to possess direct antioxidant actions against free-radical-induced oxidative stress in vitro [7][8][9][10], but it remains to be shown if the in vivo gastric protective effect of acet aminophen is due to its antioxidant effect. Superoxide radicals or hydroxyl radicals have been reported to play important roles in the pathogenesis of gastric erosions induced by ischemia-reperfusion in rats [11][12][13][14], There fore, using this model of acute gastric mucosal injury, we studied whether or not the protec tive effect of acetaminophen against ischemia-reperfusion-induced gastric injury is due to antioxidant or radical scavenging ac tions in vivo.…”

The protective mechanisms of paracetamol against ethanol-induced gastric mucosal damage in rats

“…reduces ethanol-induced gastric mucosal damage (Poon et a1 1988). As subcutaneously (s.c.)-injected paracetamol also effectively antagonizes ethanolinduced gastric lesions (Poon et al 1988), it is possible that the protective mechanism could be mediated, partly or wholly, through a systemic pathway. Somasundaram & Ganguly (1987) have shown the importance of the vagus nerve in maintaining normal levels of gastric mucus glycoproteins and, thus, mucosal integrity; absence of vagal influence weakens the mucus barrier.…”

Paracetamol potentiates stress-induced gastric ulceration in rats

“…This study demonstrates that oral administration of paracetamol 125 or 250 mg kg-', in doses which have been shown to protect against ethanol-induced lesion formation (Poon et al 1987), worsens stress-induced ulceration. Although paracetamol p.0.…”

“…However, this topical action could not be antagonized by sucralfate, which is known to enhance the integrity of the mucosal barrier and to prevent gastric damage by noxious agents (Szabo & Brown 1987). As paracetamol does not affect the mucus which adheres to the gastric mucosa (Poon et al 1987), it is possible that this drug exerts its action beyond the mucosal barrier. The drug may act through active metabolites formed in the liver (Flower et a1 1985).…”