Resveratrol, a red wine constituent polyphenol, prevents superoxide-dependent inflammatory responses induced by ischemia/reperfusion, platelet-activating factor, or oxidants.
Moderate consumption of red wine has been shown to exert cardioprotection against ischemia/reperfusion. Because oxidant-dependent leukocyte infiltration plays a critical role in ischemia/reperfusion-induced tissue injury, we hypothesized that resveratrol, a red wine constituent polyphenol would attenuate postischemic leukocyte recruitment and subsequent endothelial dysfunction. Intravital microscopic approaches were used to quantify leukocyte/endothelial cell interactions and venular protein leakage in rat mesenteries exposed to either 20 min ischemia and 60 min reperfusion (I/R), oxidants generated by the reaction of hypoxanthine and xanthine oxidase (HX/XO), platelet-activating factor (PAF), or leukotriene B4 (LTB4). I/R or HX/HX produced marked increases in the number of adherent (LA) and emigrated (LE) leukocytes, which were associated with significant increases in venular albumin leakage (VAL). Intravenous administration of resveratrol or superoxide dismutase (SOD) attenuated these increases in LA, LE, and VAL. Superfusion of the mesentery with PAF or LTB4 also markedly increased LA, LE, and VAL. While resveratrol attenuated the proinflammatory effects of PAF, LTB4-induced changes were not affected by resveratrol. Resveratrol prevents leukocyte recruitment and endothelial barrier disruption induced by a number of superoxide-dependent proinflammatory stimuli, including I/R, HX/XO, or PAF. These salutary effects appear to be related to the antioxidant properties of resveratrol and contribute to the cardioprotective actions associated with consumption of red wine.
Shigematsu
Sakuji
S
Department of Internal Medicine, Oita Medical University, Oita, Japan. sshige@oita-med.ac.jp
Ishida
Shuji
S
Hara
Masahide
M
Takahashi
Naohiko
N
Yoshimatsu
Hironobu
H
Sakata
Toshiie
T
Korthuis
Ronald J
RJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002448:Cell Adhesion; D005419:Flavonoids / Q000737:chemistry*; D005609:Free Radicals; D019271:Hypoxanthine / Q000378:metabolism; D007249:Inflammation; D007962:Leukocytes / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D016877:Oxidants / Q000378:metabolism; D010636:Phenols / Q000737:chemistry*; D010972:Platelet Activating Factor / Q000378:metabolism*; D059808:Polyphenols; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors; D014969:Xanthine Oxidase / Q000378:metabolism
D000975:Antioxidants; D005419:Flavonoids; D005609:Free Radicals; D016877:Oxidants; D010636:Phenols; D010972:Platelet Activating Factor; D059808:Polyphenols; D013267:Stilbenes; D013481:Superoxides; D007975:Leukotriene B4; D019271:Hypoxanthine; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D000077185:Resveratrol