stilbenes and Ulcer

Although resveratrol is currently being evaluated in pre-clinical studies as a potential cancer chemopreventive agent and cardiovascular stress-releasing compound, treatment with resveratrol severely delays healing of pre-existing gastric ulcers. Resveratrol treatment can also induce endothelial NOS (eNOS) expression. Here, we have attempted to modulate NO production via eNOS in order to alleviate the pro-ulcer effects of resveratrol.. Gastric ulcers were induced in mice with a single dose of indomethacin. The effects of pretreatment with l-arginine on the pro-ulcer effects of resveratrol in these mice were then assessed. We measured ulcer damage scores (DS), myeloperoxidase (MPO) activity, generation of prostaglandin E(2) (PGE(2)) and NO, along with a gene expression study.. Resveratrol significantly aggravated damage from indomethacin-induced gastric ulcers, and delayed healing, as shown by increased DS and MPO activity. The mRNA for cyclooxygenase (COX)-1, but not that for COX-2, was inhibited by resveratrol treatment, with reduced synthesis of PGE(2) by gastric tissue. However, resveratrol treatment induced eNOS gene expression and shifted the eNOS/iNOS balance. l-Arginine given before resveratrol in mice with indomethacin-induced ulcers significantly increased tissue NO synthesis and improved ulcer healing.. Exogenous l-arginine increased NO formation via raised levels of eNOS induced by resveratrol and protected against the pro-ulcer effects of resveratrol. Therefore, l-arginine might be useful for alleviation of the pro-ulcer side effects of resveratrol in patients.

Topics: Animals; Antineoplastic Agents; Arginine; Cyclooxygenase 1; Cyclooxygenase 2; Indomethacin; Male; Mice; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Resveratrol; RNA, Messenger; Stilbenes; Stomach Ulcer; Ulcer; Wound Healing

Topics: Acetazolamide; Animals; Bis-Trimethylammonium Compounds; Endopeptidases; Enzyme Precursors; Gastric Mucosa; Immobilization; Pepsinogen A; Pharmacology; Phenobarbital; Rats; Research; Stilbenes; Stomach Ulcer; Strychnos nux-vomica; Ulcer

Topics: Estradiol Congeners; Peptic Ulcer; Stilbenes; Ulcer