title: Sulforaphane protects ischemic injury of hearts through antioxidant pathway and mitochondrial K(ATP) channels.
abstract: Reactive oxygen species are important mediators that exert a toxic effect during ischemia-reperfusion (I/R) injury of various organs. Sulforaphane is known to be an indirect antioxidant that acts by inducing Nrf2-dependent phase 2 enzymes. In this study, we investigated whether sulforaphane protects heart against I/R injury. Sprague-Dawley rats received sulforaphane (500microg/kg/day) or vehicle intraperitoneally for 3 days and global ischemia was performed using isolated perfused Langendorff hearts. Hearts were perfused with Krebs-bicarbonate buffer for 20min pre-ischemic period followed by a 20min global ischemia and 50min reperfusion. Treatment with sulforaphane inhibited an increase in the post-ischemic left ventricular end-diastolic pressure (LVEDP) and improved the post-ischemic left ventricular developed pressure (LVDP), +/-dP/dt, and coronary flow as compared with the untreated control hearts. Pretreatment with 5-hydroxydecanoic acid (5-HD), a mitochondrial K(ATP) channel blocker, for 10min before ischemia attenuated the improvement of LVEDP, LVDP, +/-dP/dt, and coronary flow induced by sulforaphane. Sulforaphane markedly decreased the infarcted size and attenuated the increased lactate dehydrogenase level in effluent during reperfusion. Pretreatment with 5-HD also blocked these protective effects of sulforaphane. Post-ischemia increased the concentration of atrial natriuretic peptide in coronary effluent, which attenuated by sulforaphane treatment. Decreases on Mn-superoxide dismutase (SOD), catalase, and heme oxygenase-1 levels by I/R were increased by sulforaphane treatment and pretreatment of 5-HD blocked the sulforaphane effects. Increases in Bax and caspase-3 levels, and decrease in Bcl-2 level by I/R were attenuated by sulforaphane treatment. These results suggest that the protective effects of sulforaphane against I/R injury may be partly mediated through mitochondrial K(ATP) channels and antioxidant pathway.
authors: Department of Pharmacology, Diabetes Research Center, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors: Cheng Shi
authors: CS
authors: Piao
authors: Shan
authors: S
authors: Gao
authors: Geum-Hwa
authors: GH
authors: Lee
authors: Do Sung
authors: DS
authors: Kim
authors: Byung-Hyun
authors: BH
authors: Park
authors: Soo Wan
authors: SW
authors: Chae
authors: Han-Jung
authors: HJ
authors: Chae
authors: Suhn Hee
authors: SH
authors: Kim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D016166:Free Radical Scavengers / Q000378:metabolism; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D017879:Isothiocyanates; D054086:KATP Channels / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013454:Sulfoxides; D013861:Thiocyanates / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D003652:Decanoic Acids; D016166:Free Radical Scavengers; D006880:Hydroxy Acids; D017879:Isothiocyanates; D054086:KATP Channels; D026902:Potassium Channel Blockers; D019253:Proto-Oncogene Proteins c-bcl-2; D013454:Sulfoxides; D013861:Thiocyanates; D051028:bcl-2-Associated X Protein; C052853:5-hydroxydecanoic acid; D009320:Atrial Natriuretic Factor; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; C016766:sulforaphane