Experimental production of peptic ulcer, gastric damage and cancer models and their use in pathophysiological studies and pharmacological treatment--Polish achievements

Abstract

The common acid related diseases of the upper GI tract could be considered as primarily due to the defect in barrier function either of the gastric mucosal or duodenal epithelium leading to the formation of gastric or duodenal ulcers. An attempt was made in this chapter to discuss the history of peptic ulcer disease in humans and methods for the production of acute gastric lesions and ulcers in experimental animals with the special attention focused to the contribution of Polish scientists and investigators into this field. Early surgical advances in the management of peptic ulcers were emphasized that were then subsequently replaced by pharmacological treatment (histamine H(2)-receptor antagonists, proton pump inhibitors) and considered as the major strategy against the acid disorders. This included the immense body of work performed by numerous group of investigators, including Polish researchers, to identify the effects of acid, bile salts, aspirin and other non-steroidal anti-inflammatory drugs (NSAID), stress, Helicobacter pylori (H. pylori) infection, prostaglandins (PG) and nitric oxide (NO) on the integrity of the gastrointestinal mucosa, which all were discussed in this chapter. The concept of major defensive mechanism in the stomach called "cytoprotection", originally proposed by Andre Robert is recalled in the relevance to the great contribution of Polish scientist working at the Jagiellonian University in Cracow. These experimental studies gave a new insight into the mechanism of action of arachidonate cascade products such as PGs, tromboxanes and leukotrienes and had opened the new therapeutic avenues for the gastroprotective treatment of the acute gastric mucosal damage. Detailed studies revealed, however, that PG-induced cytoprotection offers a short-term protection against gastric lesions induced by corrosive agents but unfortunately this phenomenon gives a little, if any, impact to the process of ulcer healing. The experimental studies on healing of gastric ulcers that become supportive for the clinical trial in humans, performed also by Polish pioneers and the effect of numerous growth factors (EGF, TGF alpha), NO inhibitors, cyclooxygenase- (COX)-1 and COX-2 inhibitors and new safer derivatives of NSAID releasing NO in protection and ulcer healing are discussed. Finally, the major discovery by Warren and Marshall of H. pylori that have been studied world-wide in experimental animals including also Polish investigators, allowed for the better insight to the pathological consequences of this germ infection in the gastric mucosa and helped to establish the anti-H. pylori eradication therapy.