Mechanisms of flavonoid protection against myocardial ischemia-reperfusion injury.
Flavonoids have long been acknowledged for their unique antioxidant properties, and possess other activities that may be relevant to heart ischemia-reperfusion. They may prevent production of oxidants (e.g. by inhibition of xanthine oxidase and chelation of transition metals), inhibit oxidants from attacking cellular targets (e.g. by electron donation and scavenging activities), block propagation of oxidative reactions (by chain-breaking antioxidant activity), and reinforce cellular antioxidant capacity (through sparing effects on other antioxidants and inducing expression of endogenous antioxidants). Flavonoids also possess anti-inflammatory and anti-platelet aggregation effects through inhibiting relevant enzymes and signaling pathways, resulting ultimately in lower oxidant production and better re-establishment of blood in the ischemic zone. Finally, flavonoids are vasodilatory through a variety of mechanisms, one of which is likely interaction with ion channels. These multifaceted activities of flavonoids raise their utility as possible therapeutic interventions to ameliorate ischemia-reperfusion injury.
Akhlaghi
Masoumeh
M
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada S7N 5C9.
Bandy
Brian
B
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000627:therapeutic use; D005419:Flavonoids / Q000378:metabolism* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D014665:Vasodilator Agents / Q000378:metabolism / Q000627:therapeutic use; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007473:Ion Channels; D016877:Oxidants; D010975:Platelet Aggregation Inhibitors; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D014969:Xanthine Oxidase