EFFECTS OF CINITAPRIDE ON GASTRIC-ULCERATION AND SECRETION IN RATS

Objective and Design: The aim of the present study was to examine the effects of cinitapride, a novel prokinetic benzamide-stimulating gastr ointestinal motility agent, on gastric secretion and ulceration in rat s and elucidate some possible vascular and anti-oxidant mechanisms of such protection. Material: Male Wistar rats. Treatment: Cinitapride (C NT, Lab. Almirall, S.A.) (0.25, 0.5, and 1 mg/kg) and 5-hydroxytryptam ine (5-HT, Sigma Chemical Co., St, Louis, MO, USA) (10 mg/kg), adminis tered intraperitoneally (i.p.). Methods: Gastric ulceration was induce d by instillation of 1 mL/100 g animal of 50% (v/v) ethanol in distill ed water and by pylorus-ligated rat model. Gastric microvascular chang es, and the activity of myeloperoxidase (as a marker of neutrophil inf iltration) and glutathione peroxidase (an important enzyme in scavengi ng of lipid peroxides) were determined, The results were compared with those of 5-HT. The data were evaluated using Student's t-test for pai red data and the non-parametric Mann-Whitney U-test. Results: In 4 h p yloric-ligated animals, i.p. CNT did not significantly reduce the inci dence of gastric mucosal damage, and no significant differences were f ound in the values of total volume and acidity. However, CNT caused a marked and dose-dependent reduction of haemorrhagic lesions induced by 50% v/v ethanol. These protective effects were specifically related t o a reduction of neutrophil infiltration. CNT at the dose of 1 mg/kg r aised the decreased glutathione peroxidase activity to the control lev el. In contrast, pretreatment with 5-HT worsened the ethanol-induced e rosions, but did not significantly induce any gastric microvascular ch anges. However, the myeloperoxidase activity rose markedly and the glu tathione peroxidase levels decreased significantly in the mucosa injur ed by 50% v/v ethanol. Conclusions: This study demonstrates a new gast roprotective feature of CNT that could be partly explained not only th rough reduction of neutrophil toxicity but also by an increased synthe sis of free-radical scavenging enzymes such as glutathione peroxidase. Furthermore, it is likely that serotonergic-dependent mechanisms are also involved via 5-HT2-receptor blockade and 5-HT1 receptor activatio n.