Effects of Hypericum perforatum extract in a rat model of ischemia and reperfusion injury.
Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants, and/or a depletion of antioxidants. A considerable body of recent evidence suggests that oxidative stress and exaggerated production of reactive oxygen species play a major role in several aspects ischemia and reperfusion. Hypericum perforatum is a medicinal plant species containing many polyphenolic compounds, namely flavonoids and phenolic acids. Because polyphenolic compounds have high antioxidant potential, in this study we evaluated the effect of H. perforatum extract on splanchnic artery occlusion (SAO) shock-mediated injury. SAO shock was induced in rats by clamping the superior mesenteric artery and the celiac trunk for 45 min. After 1 h of reperfusion, SAO-shocked rats developed a significant fall in mean arterial blood pressure. Treatment of rats with H. perforatum extract (applied at 25 mg/kg 15 min before reperfusion) significantly reduced a significant fall in mean arterial blood pressure and the migration of polymorphonuclear cells caused by SAO-shock. H. perforatum extract also attenuated the ileum injury (histology) as well as the increase in the tissue levels of myeloperoxidase and malondialdehyde caused by SAO shock in the ileum. Immunohistochemical analysis for nitrotyrosine and for poly ADP-ribosylated proteins revealed a positive staining in ileum from SAO-shocked rats. The degree of staining for nitrotyrosine and poly ADP-ribosylated proteins was markedly reduced in tissue sections obtained from SAO-shocked rats that had received H. perforatum extract. Reperfused ileum tissue sections from SAO-shocked rats showed positive staining for P-selectin and for intercellular adhesion molecule-1 in the vascular endothelial cells. H. perforatum extract treatment markedly reduced the intensity and degree of P-selectin and intercellular adhesion molecule-1 in tissue section from SAO-shocked rats. H. perforatum extract treatment significantly improved survival. In conclusion, this study demonstrates that H. perforatum extract exerts multiple protective effects in splanchnic artery occlusion-reperfusion shock and suggests that H. perforatum extract may be a candidate for consideration as a therapeutic intervention for ischemia-reperfusion injury.
De Paola
Rosanna
R
Department of Clinical and Experimental Medicine and Pharmacology, Torre Biologica, Policlinico Universitario, 98123 Messina, Italy.
Muià
Carmelo
C
Mazzon
Emanuela
E
Genovese
Tiziana
T
Crisafulli
Concetta
C
Menegazzi
Marta
M
Caputi
Achille P
AP
Suzuki
Hisanori
H
Cuzzocrea
Salvatore
S
D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D001794:Blood Pressure; D016207:Cytokines / Q000378:metabolism; D003720:Densitometry; D005419:Flavonoids / Q000737:chemistry; D062385:Hydroxybenzoates / Q000737:chemistry; D020902:Hypericum / Q000378:metabolism*; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D017538:Mesenteric Artery, Superior / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism; D019007:P-Selectin / Q000737:chemistry / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010636:Phenols / Q000737:chemistry; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry; D059808:Polyphenols; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000188:drug therapy*; D012769:Shock; D013997:Time Factors; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry
D000975:Antioxidants; D016207:Cytokines; D005419:Flavonoids; D062385:Hydroxybenzoates; D019007:P-Selectin; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D017382:Reactive Oxygen Species; D018799:Intercellular Adhesion Molecule-1; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D009195:Peroxidase; D011065:Poly(ADP-ribose) Polymerases; C017616:phenolic acid