title: Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways.
abstract: OBJECTIVE
  Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown.
  
  
  METHODS
  We compared the effects of GSE on gastric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without (A) inhibition of cyclooxygenase (COX)-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, (B) suppression of NO-synthase with L-NNA (20 mg/kg ip), and (C) inactivation by capsaicin (125 mg/kg sc) of sensory nerves with or without intragastric (ig) pretreatment with GSE applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of gastric lesions were measured by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance technique and plasma gastrin levels and the gastric mucosal generation of PGE2, superoxide dismutase (SOD) activity and malonyldialdehyde (MDA) concentration, as an index of lipid peroxidation were determined.
  
  
  RESULTS
  Ethanol and WRS caused gastric lesions accompanied by the significant fall in the GBF and SOD activity and the rise in the mucosal MDA content. Pretreatment with GSE (8-64 mg/kg i g) dose-dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% (ID50) was 25 and 36 mg/kg, respectively, and this protective effect was similar to that obtained with methyl PGE2 analog (5 microg/kg i g). GSE significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma gastrin levels while attenuating MDA content. Inhibition of PGE2 generation with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the GSE-induced protection and the accompanying hyperemia. Co-treatment of exogenous calcitonine gene-related peptide (CGRP) with GSE restored the protection and accompanying hyperemic effects of GSE in rats with capsaicin denervation.
  
  
  CONCLUSIONS
  GSE exerts a potent gastroprotective activity against ethanol and WRS-induced gastric lesions via an increase in endogenous PG generation, suppression of lipid peroxidation and hyperemia possibly mediated by NO and CGRP released from sensory nerves.
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Cracow, Poland. mpbrzozo@cyf-kr.edu.pl
authors.forename: Tomasz
authors.initials: T
authors.lastname: Brzozowski
authors.forename: Peter C
authors.initials: PC
authors.lastname: Konturek
authors.forename: Danuta
authors.initials: D
authors.lastname: Drozdowicz
authors.forename: Stanislaw J
authors.initials: SJ
authors.lastname: Konturek
authors.forename: Oxana
authors.initials: O
authors.lastname: Zayachivska
authors.forename: Robert
authors.initials: R
authors.lastname: Pajdo
authors.forename: Slawomir
authors.initials: S
authors.lastname: Kwiecien
authors.forename: Wieslaw W
authors.initials: WW
authors.lastname: Pawlik
authors.forename: Eckhart G
authors.initials: EG
authors.lastname: Hahn
mesh_terms: D000818:Animals; D002492:Central Nervous System Depressants / Q000633:toxicity; D032083:Citrus paradisi / Q000737:chemistry*; D000431:Ethanol / Q000633:toxicity; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry; D013270:Stomach / Q000187:drug effects / Q000294:innervation / Q000473:pathology; D013272:Stomach Diseases / Q000188:drug therapy* / Q000378:metabolism*; D013312:Stress, Physiological / Q000150:complications; D014227:Triazines / Q000378:metabolism*
chemical_list: D002492:Central Nervous System Depressants; D010936:Plant Extracts; D014227:Triazines; D009569:Nitric Oxide; D000431:Ethanol; C011835:Grotan BK