The Effect of Cimetidine on Adaptive Cytoprotection by Mild Irritant Dose of HC1 in the Rat Gastric Mucosa

Abstract

ABSTRACT--While cimetidine (CIM) is strikingly effective in inhibiting gastric acid secretion, its effect on the defensive mechanisms of the gastric mucosa has been con troversial. The aims of the present study were to test if administration of CIM at an antisecretory dose is protective against acid-induced injury and to assess its effect on adaptive cytoprotection induced by non-necrotizing concentrations of HCl in rats. A dose of 100 mg/kg of CIM was administered once, or twice a day for 5 days intraperi toneally. To study the effect of CIM on HCl-induced damage, 0.6 N HCl was given orally one hour after the last administration of CIM. To study the effect of CIM on adaptive cytoprotection, 0.35 N HCl was given orally one hour after the last adminis tration of CIM. Fifteen minutes later, 0.6 N HCl was given orally. Thirty minutes af ter the administration of 0.6 N HCI, the stomach was removed and ulcer indices were calculated. Pretreatment with CIM did not prevent 0.6 N HCI induced gastric damage. Prior administration of 0.35 N HCI significantly reduced ulcer indices caused by 0.6 N HCI. Short or long term treatment with CIM did not have significant effects on the reduction of ulcer indices. These results suggest that CIM at an antisecretory dose neither acts as a protective agent nor modulates the protective process of the gastric mucosa.Recently histamine H2 receptor blocking agents (H2 blockers) have been widely used in the therapy of peptic ulcers. While H2 block ers are effective as ulcer-healing agents, the frequency of relapse has been reported to be relatively high (1). On the other hand, pros taglandins (PG) are important defensive agents of the gastric mucosa. Exogenously administered PG prevents gastric damage in duced by necrotizing agents (cytoprotection, 2). Low concentrations of necrotizing agents (mild irritants) also show similar effects against strong irritants by stimulation of en dogenous formation of PG (adaptive cyto protection, 3). The effect of H2 blockers on PG production has been controversial (4-7). H2 blockers might decrease endogenous PG formation or change the response of the gas tric mucosa to mild irritants. The purpose of our study was to assess the effect of short and long term administration of cimetidine at an anti-secretory dose on HCl-induced gastric damage and adaptive cytoprotection.

2,3‐Dimercaptopropanol, a thiol chelator, alleviates gastroduodenal ulcers in rats

“…[37] have shown that certain prostaglandins maintain the cellular integrity of the gastric mucosa by a mechanism other than the inhibition of gastric acid secretion. On the other hand, inhibition of gastric acid secretion failed to offer cytoprotection of gastric mucosa against necrotizing agents [38,39]. Thus, the antisecretory compounds may or may not be cytoprotective, depending on the type and severity of gastric lesions [40–42].…”