Pro-ulcer effects of resveratrol in mice with indomethacin-induced gastric ulcers are reversed by l-arginine: RESEARCH PAPER

P. Guha, A. Dey, A. Chatterjee, S. Chattopadhyay, S. K. Bandyopadhyay

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Background and purpose: 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. Experimental approach: 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. Key results: 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. Conclusions and implications: 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.

Original languageEnglish (US)
Pages (from-to)726-734
Number of pages9
JournalBritish Journal of Pharmacology
Issue number3
StatePublished - Feb 2010
Externally publishedYes


  • Gastric ulcer
  • Resveratrol
  • eNOS
  • l-NAME
  • l-arginine

ASJC Scopus subject areas

  • Pharmacology


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