Beetroot juice reduces infarct size and improves cardiac function following ischemia–reperfusion injury: Possible involvement of endogenous H₂S

Abstract

Ingestion of high dietary nitrate in the form of beetroot juice (BRJ) has been shown to exert antihypertensive effects in humans through increasing cyclic guanosine monophosphate (cGMP) levels. Since enhanced cGMP protects against myocardial ischemia-reperfusion (I/R) injury through upregulation of hydrogen sulfide (H 2 S), we tested the hypothesis that BRJ protects against I/R injury via H 2 S. Adult male CD-1 mice received either regular drinking water or those dissolved with BRJ powder (10 g/L, containing $0.7 mM nitrate). Seven days later, the hearts were explanted for molecular analyses. Subsets of mice were subjected to I/R injury by occlusion of the left coronary artery for 30 min and reperfusion for 24 h. A specific inhibitor of H 2 S producing enzymecystathionine-g-lyase (CSE), DL-propargylglycine (PAG, 50 mg/kg) was given i.p. 30 min before ischemia. Myocardial infarct size was significantly reduced in BRJ-fed mice (15.8 AE 3.2%) versus controls (46.5 AE 3.5%, mean AE standard error [SE], n ¼ 6/group, P < .05). PAG completely blocked the infarct-limiting effect of BRJ. Moreover, BRJ significantly preserved ventricular function following I/R. Myocardial levels of H 2 S and its putative protein target -vascular endothelial growth factor receptor 2 (VEGFR2) were significantly increased by BRJ intake, whereas CSE mRNA and protein content did not change. Interestingly, the BRJ-induced cardioprotection was not associated with elevated blood nitrate-nitrite levels following I/R nor induction of cardiac peroxiredoxin 5, a mitochondrial antioxidant enzyme previously linked to nitrate-induced cardioprotection. We conclude that BRJ ingestion protects against post-I/R myocardial infarction and ventricular dysfunction possibly through CSE-mediated endogenous H 2 S generation. BRJ could be a promising natural and inexpensive nutraceutical supplement to reduce cardiac I/R injury in patients.

Pre- and postconditioning the heart with hydrogen sulfide (H2S) against ischemia/reperfusion injury in vivo: a systematic review and meta-analysis

“… 30 LAD 24 R Pentobarbital SEM 6 45.5 5 6 10.2 3.9 41 Salloum et al [ 52 ] d Mouse M 32.2 ± 0.4 g Cinaciguat Post (10 µg/kg) as a bolus 5 min before reperfusion i.v. 30 LAD 24 R Pentobarbital SEM 6 43.0 1.5 6 16.5 3.7 42 Salloum et al [ 53 ] Mouse M 28–33 g Beetroot juice Pre (10 g/L) in drinking water for 7 days before ischemia p.o. 30 LAD 24 R Pentobarbital SEM 6 46.5 3.5 6 15.8 3.2 43 Sivarajah et al []55 Rat M 220–300 g NaHS Pre (3 mg/kg) as a bolus 15 min before ischemia i.p.…”

Nutraceuticals in the Treatment of Pulmonary Arterial Hypertension

“…Beet juice is commonly used as a supplement because of its high quantity of inorganic nitrate, a compound found naturally in vegetables and processed meats [ 210 ]. Nitrate is believed to produce cardiovascular benefits, such as protecting against myocardial ischemia/reperfusion, vascular dysfunction, and hypertension in mice and rats [ 211 , 212 ]. A study found decreased nitrate and increased nitrite contents in home-made raw beet, carrot, and radish juices after 48 h of storage at ambient temperatures.…”

Hydrogen Sulfide (H2S)-Releasing Compounds: Therapeutic Potential in Cardiovascular Diseases

“…This effect of alpha lipoic acid may be related to the release of sulfur sulfur and H 2 S ( Dudek et al, 2014 ). The intake of beetroot juice (BRJ) prevents myocardial infarction and ventricular dysfunction after I/R in adult male CD-1 mice through CSE-mediated endogenous H 2 S production ( Salloum et al, 2015 ). Na 2 S administration can reduce infarct size induced by myocardial I/R injury in db/db mice ( Peake et al, 2013 ).…”