Gastroprotective effects of pantoprazole against experimental mucosal damage.
The present study investigated the gastroprotective effects of the proton pump 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-HCl (ED50 = 14.1 and 21.6 micromol/kg, respectively). These effects were associated with a marked increment of Alcian blue recovery from gastric bound mucus (ED50 = 18.8 and 29.3 micromol/kg, respectively). In addition, both pantoprazole and omeprazole inhibited gastric acid secretion in pylorus-ligated rats (ED50 = 1.5 and 3.3 micromol/kg, respectively). Further experiments indicated that the protective effects of pantoprazole were not modified by L-365,260 (a gastrin receptor antagonist), suramin (a drug able to interfere with 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 (an inhibitor of prostaglandin synthesis) and fully prevented by N-ethylmaleimide (a potent blocker of sulfhydryl compounds). The present data provide histomorphometric evidence that: 1) pantoprazole is endowed with gastroprotective properties and is more active than omeprazole in preventing the necrotic mucosal damage induced by ethanol-HCl; 2) according to the rank order of ED50 values, the protective 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 availability of sulfhydryl radicals at the level of the gastric mucosa may account for the gastroprotective effects of pantoprazole.
Blandizzi
C
C
Department of Oncology, University of Pisa, Italy.
Natale
G
G
Gherardi
G
G
Lazzeri
G
G
Marveggio
C
C
Colucci
R
R
Carignani
D
D
Del Tacca
M
M
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage; D005033:Ethylmaleimide / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006851:Hydrochloric Acid / Q000008:administration & dosage; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009093:Mucus / Q000187:drug effects; D019335:Nitroarginine / Q000494:pharmacology; D009853:Omeprazole / Q000494:pharmacology; D000077402:Pantoprazole; D010671:Phenylurea Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013454:Sulfoxides / Q000494:pharmacology*; D013498:Suramin / Q000494:pharmacology
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D013454:Sulfoxides; D019335:Nitroarginine; C058121:L 365260; D000431:Ethanol; D013498:Suramin; D000077402:Pantoprazole; D009853:Omeprazole; D005033:Ethylmaleimide; D006851:Hydrochloric Acid; D007213:Indomethacin