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Basic Mechanisms of Ischemia/Reperfusion Injury Leading to Cellular and Tissue Damage: Therapeutic Implications

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Book cover Modulation of Oxidative Stress in Heart Disease

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Abstract

Produced free radicals exert their physiological function and thereafter become neutralized by antioxidants. In contrast, if they are produced in abundance, e.g., during ischemia/reperfusion (I/R), after they exhaust antioxidant reserves, they exert their harmful effect on cellular structures. The major significant reactive oxygen species (ROS) are the anion of superoxide (O2•-), the hydrogen peroxide (H2O2), and the hydroxyl radical (OH•). The collective term reactive nitrogen species (RNS) mainly includes the radical of nitric oxide (NO•), the peroxynitrite potent oxidant (ONOO−), the radical nitrogen dioxide (NO2•), and other nitrogen oxides. During ischemia, the tissue cells begin to suffer, when the oxygen delivery (DO2) to tissues decreases beyond the critical DO2 (cDO2) level, namely, when the metabolism becomes anaerobic. The cell suffering maximizes, when beta-oxidation of fatty acids is the last fuel that still feeds oxidative phosphorylation. Further drop of DO2 leads to severe ischemia with intracellular conversion of xanthine dehydrogenase to xanthine oxidase and increased concentration of xanthine and hypoxanthine. Upon reperfusion and abundant O2 reentry, free radical burst follows, with membrane destruction and massive cellular damage, mainly coming from the peroxidation of lipid bilayer arrangement. Suggested methods of I/R injury prophylaxis are the use of antioxidants, scavengers, and preconditioning techniques. The new approaches that seem to be promising focus on the progressive reentry of O2 to the thirsty for O2 ischemic tissues: initially in low concentrations of O2 to meet the low potentials of biochemical pathways to use O2 and thereafter in gradually increasing concentrations toward normal. Large, open, double blind, multicenter trials are still lacking.

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Abbreviations

ATP:

adenosine triphosphate

cNOS:

constitutive NO synthase

DO2:

oxygen delivery

GR :

glutathione reductase

GSH :

glutathione reduced

GSSG :

glutathione disulfide

iNOS:

inducible NO synthase

LTF :

lactoferrin

MBPs :

metal-binding proteins

MPO:

myeloperoxidase

NAD+/NADH:

oxidized/reduced adenine dinucleotide

NADP+/NADPH:

oxidized/reduced adenine dinucleotide phosphate

O2ER:

oxygen extraction ratio

RNS:

reactive nitrogen species

ROS:

reactive oxygen species

VO2:

oxygen consumption

XDH:

xanthine dehydrogenase

XO:

xanthine oxidase

XOR :

xanthine oxidoreductase

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Authors and Affiliations

  1. 3rd Department of Critical Care, Evgenidio Hospital, Athens University School of Medicine, Athens, Greece

    Emmanuel E. Douzinas

  2. 4th Department of Internal Medicine, Evangelismos Hospital, Athens, Greece

    Aikaterini Apeiranthitis

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  1. Emmanuel E. Douzinas
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  2. Aikaterini Apeiranthitis
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Editors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Institute of Cardiovascular Science, St. Boniface Hospital Research Centre, Winnipeg, MB, Canada

    Naranjan S. Dhalla

  3. Translational Health Science and Technology Institute, Faridabad, Haryana, India

    Madhu Dikshit

  4. Translational Health Science and Technology Institute, Faridabad, Haryana, India

    Nirmal K. Ganguly

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Douzinas, E.E., Apeiranthitis, A. (2019). Basic Mechanisms of Ischemia/Reperfusion Injury Leading to Cellular and Tissue Damage: Therapeutic Implications. In: Chakraborti, S., Dhalla, N., Dikshit, M., Ganguly, N. (eds) Modulation of Oxidative Stress in Heart Disease. Springer, Singapore. https://doi.org/10.1007/978-981-13-8946-7_27

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