Do Reactive Oxygen Species Damage or Protect the Heart in Ischemia and Reperfusion? Analysis on Experimental and Clinical Data

Overview

Journal J Biomed Res

Specialty General Medicine

Date 2023 Jul 28

PMID 37503710

Authors

Leonid N Maslov

Natalia V Naryzhnaya

Maria Sirotina

Alexandr V Mukhomedzyanov

Boris K Kurbatov

Alla A Boshchenko

Huijie Ma

Yi Zhang

Feng Fu

Jianming Pei

Viacheslav N Azev

Vladimir A Pereverzev

Affiliations

Soon will be listed here.

Abstract

The role of reactive oxygen species (ROS) in ischemic and reperfusion (I/R) injury of the heart has been discussed for more than 40 years. It has been demonstrated that reperfusion triggers a multiple increase in free radical generation in the isolated heart. Antioxidants were found to have the ability to mitigate I/R injury of the heart. However, it is unclear whether their cardioprotective effect truly depends on the decrease of ROS levels in myocardial tissues. Since high doses and high concentrations of antioxidants were experimentally used, it is highly likely that the cardioprotective effect of antioxidants depends on their interaction not only with free radicals but also with other molecules. It has been demonstrated that the antioxidant N-2-mercaptopropionyl glycine or NDPH oxidase knockout abolished the cardioprotective effect of ischemic preconditioning. Consequently, there is evidence that ROS protect the heart against the I/R injury.

Citing Articles

O-GlcNAcylation in ischemic diseases.

Shi R, He T, Lin M, Xu J, Gu J, Xu H Front Pharmacol. 2024; 15:1377235.

PMID: 38783961 PMC: 11113977. DOI: 10.3389/fphar.2024.1377235.

Editorial commentary on the special issue of cardiovascular diseases.

Board E J Biomed Res. 2023; 37(4):229.

PMID: 37503709 PMC: 10387749. DOI: 10.7555/JBR.37.20230800.

References

Yoshida T, Maulik N, Engelman R, Ho Y, Das D . Targeted disruption of the mouse Sod I gene makes the hearts vulnerable to ischemic reperfusion injury. Circ Res. 2000; 86(3):264-9. DOI: 10.1161/01.res.86.3.264. View

Braunersreuther V, Montecucco F, Asrih M, Ashri M, Pelli G, Galan K . Role of NADPH oxidase isoforms NOX1, NOX2 and NOX4 in myocardial ischemia/reperfusion injury. J Mol Cell Cardiol. 2013; 64:99-107. DOI: 10.1016/j.yjmcc.2013.09.007. View

Zakirova A, Ivanova M, Golubiatnikov V, Mishchenko N, Koltsova E, Fedoreev S . [Pharmacokinetics and clinical efficacy of histochrome in patients with acute myocardial infarction]. Eksp Klin Farmakol. 1998; 60(6):21-4. View

Farber N, Vercellotti G, JACOB H, Pieper G, Gross G . Evidence for a role of iron-catalyzed oxidants in functional and metabolic stunning in the canine heart. Circ Res. 1988; 63(2):351-60. DOI: 10.1161/01.res.63.2.351. View

Cadenas S . ROS and redox signaling in myocardial ischemia-reperfusion injury and cardioprotection. Free Radic Biol Med. 2018; 117:76-89. DOI: 10.1016/j.freeradbiomed.2018.01.024. View

Bell R, Cave A, Johar S, Hearse D, Shah A, Shattock M . Pivotal role of NOX-2-containing NADPH oxidase in early ischemic preconditioning. FASEB J. 2005; 19(14):2037-9. DOI: 10.1096/fj.04-2774fje. View

Shafiei E, Bahtoei M, Raj P, Ostovar A, Iranpour D, Akbarzadeh S . Effects of N-acetyl cysteine and melatonin on early reperfusion injury in patients undergoing coronary artery bypass grafting: A randomized, open-labeled, placebo-controlled trial. Medicine (Baltimore). 2018; 97(30):e11383. PMC: 6078764. DOI: 10.1097/MD.0000000000011383. View

Zweier J, Flaherty J, WEISFELDT M . Direct measurement of free radical generation following reperfusion of ischemic myocardium. Proc Natl Acad Sci U S A. 1987; 84(5):1404-7. PMC: 304438. DOI: 10.1073/pnas.84.5.1404. View

Romson J, Hook B, Kunkel S, Abrams G, Schork M, Lucchesi B . Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog. Circulation. 1983; 67(5):1016-23. DOI: 10.1161/01.cir.67.5.1016. View

10.

Nozari Y, Eshraghi A, Talasaz A, Bahremand M, Salamzadeh J, Salarifar M . Protection from Reperfusion Injury with Intracoronary N-Acetylcysteine in Patients with STEMI Undergoing Primary Percutaneous Coronary Intervention in a Cardiac Tertiary Center. Am J Cardiovasc Drugs. 2018; 18(3):213-221. DOI: 10.1007/s40256-017-0258-8. View

11.

Naslund U, Haggmark S, Johansson G, Marklund S, Reiz S, Oberg A . Superoxide dismutase and catalase reduce infarct size in a porcine myocardial occlusion-reperfusion model. J Mol Cell Cardiol. 1986; 18(10):1077-84. DOI: 10.1016/s0022-2828(86)80294-2. View

12.

Zweier J, Broderick R, Kuppusamy P, Lutty G . Determination of the mechanism of free radical generation in human aortic endothelial cells exposed to anoxia and reoxygenation. J Biol Chem. 1994; 269(39):24156-62. View

13.

Tang X, Takano H, Rizvi A, F Turrens J, Qiu Y, Wu W . Oxidant species trigger late preconditioning against myocardial stunning in conscious rabbits. Am J Physiol Heart Circ Physiol. 2001; 282(1):H281-91. DOI: 10.1152/ajpheart.2002.282.1.H281. View

14.

Bolli R, Jeroudi M, Patel B, Aruoma O, Halliwell B, Lai E . Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion. Evidence that myocardial "stunning" is a manifestation of reperfusion injury. Circ Res. 1989; 65(3):607-22. DOI: 10.1161/01.res.65.3.607. View

15.

Chen E, Bittner H, Davis R, Van Trigt P, Folz R . Physiologic effects of extracellular superoxide dismutase transgene overexpression on myocardial function after ischemia and reperfusion injury. J Thorac Cardiovasc Surg. 1998; 115(2):450-8; discussion 458-9. DOI: 10.1016/s0022-5223(98)70289-2. View

16.

Garlick P, Davies M, Hearse D, Slater T . Direct detection of free radicals in the reperfused rat heart using electron spin resonance spectroscopy. Circ Res. 1987; 61(5):757-60. DOI: 10.1161/01.res.61.5.757. View

17.

Sochman J, Vrbska J, Musilova B, Rocek M . Infarct Size Limitation: acute N-acetylcysteine defense (ISLAND trial): preliminary analysis and report after the first 30 patients. Clin Cardiol. 1996; 19(2):94-100. DOI: 10.1002/clc.4960190205. View

18.

Chen J, Zeng H, Tuo Q, Yu H, Meyrick B, Aschner J . NADPH oxidase modulates myocardial Akt, ERK1/2 activation, and angiogenesis after hypoxia-reoxygenation. Am J Physiol Heart Circ Physiol. 2007; 292(4):H1664-74. PMC: 2383323. DOI: 10.1152/ajpheart.01138.2006. View

19.

Matsushima S, Tsutsui H, Sadoshima J . Physiological and pathological functions of NADPH oxidases during myocardial ischemia-reperfusion. Trends Cardiovasc Med. 2014; 24(5):202-5. PMC: 4119873. DOI: 10.1016/j.tcm.2014.03.003. View

20.

Gallagher K, Buda A, Pace D, Gerren R, Shlafer M . Failure of superoxide dismutase and catalase to alter size of infarction in conscious dogs after 3 hours of occlusion followed by reperfusion. Circulation. 1986; 73(5):1065-76. DOI: 10.1161/01.cir.73.5.1065. View