Effect of ellagic acid on gastric damage induced in ischemic rat stomachs following ammonia or reperfusion.
We examined the effect of ellagic acid (EA), one of the polyphenols that are abundantly contained in whisky as a nonalcoholic component, on gastric lesions induced by ammonia plus ischemia or ischemia/reperfusion in rats, in relation to the antioxidative system. Under urethane anesthesia, a rat stomach was mounted in an ex vivo chamber, and the following two experiments were performed; 1) a stomach was made ischemic (1.5 ml/100 g body weight) for 20 min, followed by reperfusion for 15 min in the presence of 100 mM HCl; 2) a stomach was made ischemic by bleeding from the carotid artery (1 ml/100 g body weight), followed by intragastric application of ammonia (NH4OH: 120 mM). EA (0.1-10 mg/ml) was applied in the chamber 30 min before the onset of ischemia. Gastric potential difference (PD) and mucosal blood flow (GMBF) were measured before, during and after 20 min of ischemia. Ischemia/reperfusion caused a profound drop in GMBF followed by a return, and resulted in hemorrhagic lesions in the stomach in the presence of 100 mM HCI. These lesions were dose-dependently prevented by EA with suppression of lipid peroxidation but no effect on GMBF, and the effect at 6 mg/ml was almost equivalent to that of superoxide dismutase (SOD: 15000 unit/kg/hr) infused i.v. during a test-period. On the other hand, application of NH4OH to the ischemic stomach produced a marked reduction in PD, resulting in severe hemorrhagic lesions. These changes were prevented with both EA and SOD. In addition, EA had a potent scavenging action against monochloramine in vitro. These results suggest that EA exhibits gastric protective action against gastric lesions induced by NH4OH or reperfusion in the ischemic stomach, probably due to its anti-oxidative activity. This property of EA partly explains the less damaging effect of whisky in the stomach and may be useful as the prophylactic for Helicobacter pylori-associated gastritis.
Iino
Taeko
T
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Japan.
Tashima
Kimihito
K
Umeda
Masakazu
M
Ogawa
Yoshihiro
Y
Takeeda
Masanori
M
Takata
Kanji
K
Takeuchi
Koji
K
D000641:Ammonia / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004610:Ellagic Acid / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000098:blood supply* / Q000473:pathology; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000517:prevention & control*; D013276:Stomach Ulcer / Q000517:prevention & control; D013654:Taurine / Q000494:pharmacology
D000975:Antioxidants; D004610:Ellagic Acid; D013654:Taurine; D000641:Ammonia