TY - JOUR
T1 - Pro-ulcer effects of resveratrol in mice with indomethacin-induced gastric ulcers are reversed by l-arginine
T2 - RESEARCH PAPER
AU - Guha, P.
AU - Dey, A.
AU - Chatterjee, A.
AU - Chattopadhyay, S.
AU - Bandyopadhyay, S. K.
PY - 2010/2
Y1 - 2010/2
N2 - 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.
AB - 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.
KW - Gastric ulcer
KW - NSAID
KW - Resveratrol
KW - eNOS
KW - l-NAME
KW - l-arginine
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U2 - 10.1111/j.1476-5381.2009.00572.x
DO - 10.1111/j.1476-5381.2009.00572.x
M3 - Article
C2 - 20067468
AN - SCOPUS:76449122383
SN - 0007-1188
VL - 159
SP - 726
EP - 734
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 3
ER -