Gastroprotective effects of pantoprazole against experimental mucosal damage

The present study investigated the gastroprotective effects of the proton p ump inhibitor pantoprazole on gastric mucosal damage induced by ethanol-HCl in rats. Omeprazole was used as reference drug. The morphometric analysis of gastric histological sections revealed that pantoprazole and omeprazole dose-dependently prevented the necrotic mucosal injury evoked by ethanol-HC l (ED50 = 14.1 and 21.6 mu mol/kg, respectively). These effects were associ ated with a marked increment of Alcian blue recovery from gastric bound muc us (ED50 = 18.8 and 29.3 mu mol/kg, respectively). In addition, both pantop razole and omeprazole inhibited gastric acid secretion in pylorus-ligated r ats (ED50 = 1.5 and 3.3 mu mol/kg, respectively). Further experiments indic ated that the protective effects of pantoprazole were not modified by L-365 ,260 (a gastrin receptor antagonist), suramin (a drug able to interfere wit h endogenous growth factors), N-G-nitro-L-arginine (an inhibitor of nitric oxide synthase) or systemic ablation of capsaicin-sensitive sensory nerves, whereas they were partly blocked by indomethacin tan inhibitor of prostagl andin synthesis) and fully prevented by N-ethylmaleimide (a potent blocker of sulfhydryl compounds). The present data provide histomorphometric eviden ce that: 1) pantoprazole is endowed with gastroprotective properties and is more active than omeprazole in preventing the necrotic mucosal damage indu ced by ethanol-HCl; 2) according to the rank order of ED50 values, the prot ective effects of both drugs appear to depend mainly on the enhancement of the gastric mucosal barrier rather than on the inhibition of acid secretion ; 3) an increased production of prostaglandins, as well as an increased ava ilability of sulfhydryl radicals at the level of the gastric mucosa may acc ount for the gastroprotective effects of pantoprazole. (C) 2000 Editions sc ientifiques et medicales Elsevier SAS.