Sulforaphane protects ischemic injury of hearts through antioxidant pathway and mitochondrial K(ATP) channels.
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.
Piao
Cheng Shi
CS
Department of Pharmacology, Diabetes Research Center, Chonbuk National University Medical School, Jeonju, Republic of Korea.
Gao
Shan
S
Lee
Geum-Hwa
GH
Kim
Do Sung
DS
Park
Byung-Hyun
BH
Chae
Soo Wan
SW
Chae
Han-Jung
HJ
Kim
Suhn Hee
SH
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
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