Gastroprotective effect of lupeol on ethanol-induced gastric damage and the underlying mechanism.
The effect of lupeol, a natural pentacyclic triterpene on ethanol-induced gastric damage in mice was evaluated. The gastroprotection was assessed by determination of changes in mean gastric lesion area, quantification of mucosal non-protein sulfhydryls (NP-SH), and characterized using drugs that influence the endogenous prostaglandins, alpha(2)-adrenoceptors, nitric oxide, K(ATP)-channels, and intracellular calcium. Orally administered lupeol (3, 10, and 30 mg/kg) significantly and dose-dependently attenuated the ethanol-induced gastric damage by 39-69%, whereas the positive control N-acetylcysteine (NAC, 300 mg/kg, i.p.) afforded 32% protection. Both lupeol and NAC restored the NP-SH depleted by ethanol but the lupeol effect was only marginal. Lupeol gastroprotection was attenuated by indomethacin and L-NAME, the respective COX and NO-synthase inhibitors and was weakly sensitive to alpha(2)-adrenergic antagonist yohimbine and K(ATP)-channel blocker glibenclamide, but more profoundly to calcium blocker verapamil. These pharmacological effects of lupeol may synergistically contribute to alleviating the ethanol-associated gastric damage, which is multifactorial.
Lira
Silvéria Regina de S
SR
Department of Physiology and Pharmacology, Federal University of Ceará, Rua Cel Nunes de Melo-1127, Caixa Postal-3157, Fortaleza, CE, 60430-270, Brazil.
Rao
Vietla Satyanarayana
VS
Carvalho
Ana Carla S
AC
Guedes
Marjorie M
MM
de Morais
Talita C
TC
de Souza
Antonia L
AL
Trevisan
Maria Teresa S
MT
Lima
Alana F
AF
Chaves
Mariana H
MH
Santos
Flávia A
FA
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D000094042:Lupanes
D000111:Acetylcysteine; D000893:Anti-Inflammatory Agents; D002118:Calcium; D002492:Central Nervous System Depressants; D000431:Ethanol; D054086:KATP Channels; D009569:Nitric Oxide; D053978:Pentacyclic Triterpenes; D011453:Prostaglandins; D018341:Receptors, Adrenergic, alpha-2; D013438:Sulfhydryl Compounds; D014315:Triterpenes; C010480:lupeol; D000094042:Lupanes