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Compendium August 2012 (Vol 34, No 8)

Mechanisms of Oxidative Injury in Equine Disease

by David Wong, DVM, MS, DACVIM, DACVECC, Rustin M. Moore, DVM, PhD, DACVS, Charles Brockus, DVM, PhD, DACVIM, DACVP

    CETEST This course is approved for 3.0 CE credits

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    Oxygen is essential to aerobic life, but it is also associated with the production of highly reactive compounds that can pose danger to physiologic systems when the oxygen concentration is excessive. Reactive oxygen species (ROS) are required for normal physiologic processes, but when produced in excess, they can overwhelm endogenous antioxidants, resulting in significant cellular damage and, eventually, cell death. Ischemic events can initiate numerous pathophysiologic mechanisms leading to increased production of ROS, loss of cellular energy production, and lipid peroxidation. Although reperfusion is a necessary step in cellular recovery from ischemia, it can be deleterious by leading to the generation of even more ROS and stimulating the accumulation of neutrophils. Both of these processes may contribute to irreversible cell death and, ultimately, organ failure. This article reviews oxygen metabolism, ischemia, and reperfusion injury and how these processes may occur in equine disorders.

    Click here to read the companion article: "Intestinal Ischemia-Reperfusion Injury in Horses: Pathogenesis and Therapeutics."

    Oxygen is vital for mammalian survival because of its critical role in supporting life-sustaining energy production. However, it is often overlooked that oxygen and its derivatives can paradoxically act as highly reactive compounds within the body, posing danger to life.1,2 Although the generation of reactive oxygen species (ROS) is required for numerous normal physiologic functions, oxidative stress occurs when endogenous antioxidants and oxygen scavengers are overwhelmed by ROS, resulting in cellular injury and, possibly, cell death.3 Excessive ROS are also generated and released during restoration of blood flow/perfusion (reperfusion) to previously ischemic cells (ischemia-reperfusion [IR] injury), which, along with concurrent release of various cytokines and resultant emigration of neutrophils, can further damage previously ischemic cells. A large amount of research and associated literature regarding oxidative stress and IR injury is available because of the relatively high prevalence of these pathophysiologic mechanisms (e.g., oxidative injury to the myocardium, kidneys, liver, and central nervous system) in people. Comparatively less equine-specific research is available on this topic. However, a relatively closely investigated topic is the deleterious effects of intestinal IR injury in horses with intestinal vascular compromise (i.e., strangulating obstruction of the intestines).4–6 In horses, oxidative stress may also play a role in recurrent airway obstruction, osteoarthritis, equine motor neuron disease, equine degenerative myeloencephalopathy, nutritional myodegeneration (white muscle disease), laminitis, pituitary pars intermedia dysfunction, endometritis, and negative effects of prolonged, strenuous exercise  (TABLE 1) .6–12 Hypoxic-ischemic encephalopathy (HIE) may also involve oxidative injury to the neonatal foal brain.13,14 While HIE may primarily be associated with peripartum hypoxia, ischemia, and/or asphyxia, equine-specific research on HIE is sparse and the exact pathophysiology is unknown. This article discusses the pathophysiologic mechanisms of oxidative stress and IR injury.

    Before a discussion of oxygen metabolism and toxicity, a brief review of the reduction-oxidation reaction is necessary. An oxidation reaction involves a chemical reaction between oxygen and another chemical species (FIGURE 1) . Specifically, an oxidation reaction involves the loss of electrons from an atom or a molecule by transfer to another atom or molecule. The atom or molecule that removes the electron is known as an oxidizing agent, an oxidant, or an oxidizer (e.g., oxygen).15 Conversely, a reduction reaction involves the acquisition of electrons by an atom or a molecule; the atom or molecule that donates the electrons is known as a reducing agent or a reductant.15 Because oxidation of one molecule depends on the reduction of another molecule, the overall reaction is known as a redox reaction. When carbon-based organic molecules are oxidized by oxygen, the organic molecules are degraded into smaller molecules, resulting in combinations of oxygen, carbon, and hydrogen atoms, which are principally carbon dioxide and water.15

    Oxygen Metabolism

    Oxygen is essential to life because of its vital role in adenosine triphosphate (ATP) production via oxidative phosphorylation.15 However, oxygen also is a weak oxidizing agent, and some oxygen metabolites serve as potent oxidants capable of causing widespread cellular injury. In its natural molecular or ground state, oxygen is a diatomic molecule (i.e., O2). Each oxygen molecule has an outer shell with orbitals that are occupied by electrons  (FIGURE 2) . One of oxygen’s orbitals contains two electrons spinning in opposite directions; the other two orbitals each contain a single electron that spins in the same direction as the other electron.15 Thus, the orbital with paired electrons spinning in opposite directions obeys a basic tenet of quantum atoms: an electron orbital can be occupied by two electrons only if they spin in opposite directions.15,16 Conversely, orbitals that contain only one electron are unpaired or only half full. An atom or molecule that is capable of independent existence (i.e., free) and has one or more unpaired electrons in the outer orbital is known as a free radical.3 Free radicals can be highly reactive because of their unpaired electrons, but not all free radicals are highly reactive (e.g., the oxygen molecule).1 Although oxygen has two unpaired electrons, it has weak reactivity because of the direction of the orbital spin.1,3 No two electrons can occupy the same orbital if they spin in the same direction. Therefore, an electron pair cannot be added to oxygen because one orbital would have two electrons with the same directional spin.15 This restriction limits oxygen to single electron additions.15

    Under normal circumstances, as oxygen is utilized in oxidative phosphorylation, it is reduced to water.3 This process requires the addition of four electrons and four protons (FIGURE 2) . Through this process, other ROS are produced. In the first reaction, an electron is added to oxygen in its ground state, forming the superoxide radical (O2).3,5,17,18 Although the superoxide radical has one unpaired electron, it is not considered a highly reactive radical or potent oxidant.1 The second reaction involves the addition of another electron and two protons (H+), resulting in the generation of hydrogen peroxide (H2O2).3,5,17,18 Hydrogen peroxide is not a free radical but can cross cell membranes and act as a potent cytotoxin, inactivating enzymes via oxidation of essential thiol groups.19 Because not all molecules that cause oxidative injury are free radicals, such as hydrogen peroxide, ROS is a more inclusive term.1 The hydrogen peroxide molecule is held together weakly by oxygen bonds. Because these bonds readily break, two hydroxyl radicals, each with an unpaired electron, are formed. In this third reaction (Fenton reaction), an electron is donated by ferrous iron (Fe[II]) to form a hydroxyl ion (OH-) and hydroxyl radical (OH).3,5,17,18 The hydroxyl radical is one of the most highly reactive biologic molecules and can react with another chemical species within five molecular diameters from its point of origin.1,3 The fourth and final reaction involves the addition of another electron and two protons to the hydroxyl radical, yielding two molecules of water (H2O).3,5,17,18 In healthy animals, the generation of free radicals is minimal because of highly efficient electron transfer and sequestration of metal ions (e.g., iron, copper) to proteins.1 Accordingly, approximately 90% to 95% of oxygen passing through mitochondria is converted to water; the remaining 5% to 10% escapes into the cytoplasm to form ROS.1,17 In summary, the metabolism of one molecule of oxygen requires four chemical reactions and produces three potentially reactive compounds: superoxide radical, hydrogen peroxide, and hydroxyl radical. Other sources of ROS include cytochrome P450 within the endoplasmic reticulum, cyclooxygenase, lipoxygenase, myeloperoxidase, glucose oxidase, nitric oxide (NO) synthase, xanthine oxidase (XO), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and neutrophils and monocytes during phagocytosis.1,3,20,21

    The above description of the metabolism of oxygen into water is simplified. In actuality, some of the intermediate metabolites can react with other molecules, forming various products.2 For example, the superoxide radical may react with NO to produce peroxynitrite radical (ONOO), a highly reactive radical (reactive nitrogen species [RNS]) that can either cause direct tissue damage or decompose to form hydroxyl radicals and nitrogen dioxide, also resulting in tissue injury.1,3,16 Hydrogen peroxide can react with the chloride anion, forming hypochlorous acid (HOCl), as occurs within the neutrophil phagosome with the aid of the enzyme myeloperoxidase.18,19 In addition, the oxidation of membrane lipids by ROS results in the formation of peroxyl radicals (RO2) during lipid peroxidation (FIGURES 3 and 4) .18,22 Lipids are frequently damaged by ROS because of their ubiquitous presence in cell membranes.22 Lipid peroxidation (oxidant injury to cell membranes) can result in significant structural damage to the cell membrane and occurs because of the abundance of polyunsaturated fatty acids (PUFAs; e.g., linoleic, linolenic, and arachidonic acids) within the phospholipids of mammalian cell membranes.1,18 Cellular PUFAs have unsaturated carbon-to-carbon double bonds that are especially susceptible to oxidant injury.18,22 In addition, sulfhydryl groups that cross-link cell membrane phospholipids to membrane-associated proteins (enzymes, receptors, ion channels) are also vulnerable to oxidant injury, resulting in altered conformation and function of these proteins.18 When ROS are formed, they can either react with another free radical to form a stable molecule or react with and steal an electron from a nonradical (e.g., a PUFA). When the latter occurs, the nonradical (the PUFA) is transformed into a free radical. Thus, the interaction of a radical with a nonradical creates another radical, resulting in a chain reaction that can eventually result in cell membrane damage22  (FIGURES 3 and 4) . Hydroxyl radicals and peroxynitrite are most commonly incriminated in the initiation of lipid peroxidation.2,17 ROS can also react with other biologic molecules, such as proteins, carbohydrates, nucleic acids, and DNA, resulting in structural damage and dysfunction.3,23

    Although the detrimental effects of ROS are commonly highlighted, ROS are important in normal physiologic processes. For example, ROS activate cellular growth factors, eliminate dysfunctional proteins via oxidation, and participate in cell signaling, apoptosis, and immune functions.1,3 Likewise, lipid peroxidation is a normal process, when controlled, that is necessary for disassembly of cellular membranes, pinocytosis, and arachidonic acid metabolism.18 To counter excessive oxidant injury, the body generates and uses numerous and diverse endogenous antioxidant proteins and enzymes.24 Antioxidants slow or inhibit free radical–mediated oxidative reactions through various mechanisms. For instance, the cell membrane specifically contains the antioxidant α-tocopherol (vitamin E) to arrest lipid peroxidation (FIGURES 3 and 4) . As the chain reaction of lipid peroxidation traverses the cell membrane, it interacts with α-tocopherol.18,24 Subsequently, α-tocopherol is oxidized to a poorly reactive free radical, sparing further damage to adjacent PUFAs, thus halting the progression of lipid peroxidation. Ascorbate (vitamin C) then reacts with the α-tocopherol radical, forming a weakly reactive ascorbate radical; α-tocopherol is regenerated in the process.18,24 Additional antioxidant proteins include albumin, haptoglobin, ceruloplasmin, and ferritin, which are present in the blood.6 Intracellular enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, protect the intracellular environment. Superoxide dismutase facilitates the conversion of a superoxide radical to hydrogen peroxide, whereas catalase and glutathione peroxidase reduce hydrogen peroxide to water.18,24 Nonenzymatic antioxidants include ascorbate, α-tocopherol, zinc, selenium, β-carotene, ubiquinol, and lycopene.24 Oxidative stress describes an imbalance in which formation of ROS exceeds the neutralizing capacity of endogenous antioxidants, resulting in cellular injury and activation of pathologic pathways.6,24 Therefore, oxidative stress may result from increased formation of ROS, decreased antioxidant availability, or both.

    Ischemia-Reperfusion Injury

    Ischemia entails a substantial reduction or absolute arrest of blood flow as a consequence of functional constriction or physical obstruction of blood vessels, compromising tissue perfusion as well as oxygen delivery to an organ.5,6 Oxygen plays a critical role in energy production and, in turn, normal cellular survival and function; thus, reduced oxygen delivery results in progressively inadequate ATP production and impeded homeostatic and metabolic functions. Sustained and sufficiently severe reduced oxygen delivery can result in cell death. Aside from inadequate provision of oxygen, accumulation of metabolites (e.g., ROS) directly or through mediators also causes cellular damage.5,25,26 Not surprisingly, ischemia has the most significant effect on organs that maintain a high metabolic demand, such as the intestines, kidneys, and brain.17 Once blood flow falls below a critical point of supplying an adequate amount of oxygen, oxygen stores become depleted, the ATP concentration decreases, and anaerobic glycolysis occurs in an attempt to maintain basal cell function (FIGURE 5) . Concurrently, more lactate is generated in this anaerobic environment to regenerate nicotinamide adenine dinucleotide (NADH to NAD+), which is necessary for glycolysis to continue in the absence of oxygen.27,28 Increased lactate decreases intracellular pH, further inhibiting ATP production.5,17 Cellular swelling occurs as energy deprivation reduces the activity of energy-dependent membrane ion pumps that normally maintain ionic balance.29 Concurrently, influx of calcium increases intracellular calcium concentration, resulting in altered cellular reactions and activation of cellular enzymes such as phospholipase A2 (PLA2) and calpain.5,26,29,30 As this process progresses, the cell begins to fail and lysosomes eventually release degradative enzymes, causing autolysis of cellular organelles and cell death. With a sustained ischemic event, widespread cell death culminates in the demise of the surrounding tissue and the organ.

    In instances of ischemia in which cellular integrity has not reached a point of irreparable damage, restoration of adequate blood flow can paradoxically result in further cell damage, the phenomenon known as IR injury. Reperfusion and provision of oxygen to ischemic cells is an undeniable necessity but can result in varying degrees of further damage because of various noxious metabolites, including ROS, which accumulate during ischemia.4,5 Concurrent activation of protein kinases results in the activation of nuclear factor κβ, protein activator 1, and other cellular pathways.23,29,31 The ensuing products of these transcription factors induce enzymes (inducible nitric oxide synthase [iNOS], PLA2, cyclooxygenase), cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-1, IL-6), chemokines (IL-8), and adhesion molecules (intracellular adhesion molecule 1), further contributing to IR injury.23,26,32

    Another component of IR injury involves xanthine dehydrogenase (XDH), an enzyme in most cells. In healthy animals, XDH converts hypoxanthine to xanthine and uric acid using NAD, which is then eliminated by the kidneys (FIGURE 5) .23,26 In this reaction, NAD is converted to NADH. During ischemia, oxidative phosphorylation becomes uncoupled, thus decreasing cellular ATP production. Electrons from the uncoupled reactions subsequently leak from the mitochondria. Simultaneously, metabolism of existing ATP results in accumulation of hypoxanthine, as demonstrated in one study in which 2 hours of partial ischemia reduced ATP concentrations to approximately 40% of pre-ischemia concentrations.25,33 This decline in ATP was associated with a sevenfold increase in adenosine monophosphate concentrations and a 10-fold increase in hypoxanthine concentrations within intestinal tissue.33 Additionally, XDH is converted to XO because of increased intracellular calcium and the activation of the calcium-dependent protease calpain.1,23,26 During reperfusion and reoxygenation, accumulated hypoxanthine is metabolized by XO to form xanthine. However, XO utilizes oxygen rather than NAD as a substrate, forming a large number of superoxide radicals.5,6,23

    Attention should also be directed to the role of NO in IR injury. NO, which is formed by the reaction between l-arginine and molecular oxygen and is catalyzed by NOS, can exert cytoprotective or cytotoxic cellular effects, depending on its amount, duration, source, and timing of production.1,17,26 Three distinct genes encode different isoforms of NOS: neuronal NOS, endothelial NOS, and iNOS.26 NO produced by neuronal NOS serves as a neurotransmitter in the peripheral and central nervous systems, whereas endothelial NOS regulates vascular tone by generating NO in blood vessels; these constitutive forms of NOS are critical for normal physiology.1,26,34 iNOS is expressed in response to various stimuli, including hypoxia and cytokines (interferon-γ, interleukin-1, TNF-α), by fibroblasts, macrophages, neutrophils, and vascular smooth muscle cells, thereby generating a large amount of NO, which contributes to the pathophysiology of IR injury.26,34–36 When iNOS transcription is increased because of these stimuli, particularly during hypoxia, NO generation may not increase because oxygen is a necessary substrate.17 During reperfusion, the provision of oxygen results in increased generation of NO, which can be cytotoxic at high concentrations.36 In addition, free radicals are produced when NO, which is formed from iNOS, combines with superoxide anions to form peroxynitrite radicals (ONOO).17,26 Peroxynitrite is bactericidal to certain pathogens and serves as a host defense mechanism but can also cause appreciable tissue damage during IR.36 NO can also be converted to other RNS, including nitrosonium cations and nitroxyl anions, resulting in further damage.1 Thus, as endogenous antioxidants are overwhelmed, the ROS produced during reperfusion (superoxide radical, peroxynitrite) results in further cellular damage through oxidative stress. As noted above, lipid peroxidation of membranes by ROS and RNS results in progressive cellular membrane damage, loss of selective membrane permeability, damage to DNA, and degradation of proteins and membrane-bound enzymes.6

    The accumulation of neutrophils is also an important contributor to IR injury and has been demonstrated in equine models of intestinal IR injury.5,25,37,38 Several mediators serve directly or indirectly as chemotaxis signals for neutrophil emigration, including XO, arachidonic acid metabolites, and ROS.5,6,23,26 Lipid peroxidation of cell membranes and local release of TNF-α at the site of IR are also stimuli for neutrophil immigration and sequestration via the upregulation and expression of adhesion molecules on endothelial cells and neutrophils.23,39 As neutrophils emigrate into the tissues, their proteolytic and oxidative properties further damage recovering ischemic cells and endothelium.5,17,26,37,38 As part of the respiratory burst, neutrophils utilize myeloperoxidase to produce HOCl, a highly toxic compound formed from hydrogen peroxide and chloride ions.19 Therefore, neutrophils contribute significantly to mucosal and microvascular injury.5,17,25,26 Moreover, a large number of neutrophils may accumulate, coupled with interstitial edema and platelet aggregation, resulting in obstruction of capillaries, which is known as the no-reflow phenomenon.40,41 Thus, a degree of tissue and microvascular injury observed after IR injury is a result of the accumulation of neutrophils as well as their destructive properties.17,32 Blood flow may be diminished or absent despite resolution of vascular occlusion because of excessive neutrophil accumulation, endothelial edema, and platelet and fibrin microthrombi.41


    While oxygen is necessary for aerobic organisms, the risk of oxidative stress and injury should not be overlooked. Oxidative injury is clearly involved in several disease entities in equine medicine. Thus, knowledge of the basic tenets of oxygen metabolism and antioxidants is important for equine practitioners. Likewise, an awareness of IR may provide a better understanding of the pathophysiologic mechanisms that may occur in IR injury in horses. More detailed information on oxidative stress and IR injury is available in the literature.17,34,36,39,42–45

    Downloadable PDF

    1. Fatokun AA, Stone TW, Smith RA. Oxidative stress in neurodegeneration and available means of protection. Front Biosci 2008;13:3288-3311.

    2. Freeman B. Free radical chemistry of nitric oxide: looking at the dark side. Chest 1994;105:79S-84S.

    3. Kulkarni AC, Kuppusamy P, Parinandi N. Oxygen, the lead actor in the pathophysiologic drama: enactment of the trinity of normoxia, hypoxia, and hyperoxia in disease and therapy. Antioxid Redox Signal 2007;9:1717-1730.

    4. Moore RM. Clinical relevance of intestinal reperfusion injury in horses. J Am Vet Med Assoc 1997;211:1362-1366.

    5. Moore RM, Muir WW, Granger DN. Mechanisms of gastrointestinal ischemia-reperfusion injury and potential therapeutic interventions: a review and its implications in the horse. J Vet Intern Med 1995;9:115-132.

    6. Soffler C. Oxidative stress. Vet Clin North Am Equine Pract 2007;23:135-157.

    7. Gandini G, Fatzer R, Mariscoli M, et al. Equine degenerative myeloencephalopathy in five Quarter horses: clinical and neuropathological findings. Equine Vet J 2004;36:83-85.

    8. Mayhew IG, Brown CM, Stowe HD, et al. Equine degenerative myeloencephalopathy: a vitamin E deficiency that may be familial. J Vet Intern Med 1987;1:45-50.

    9. Miller MM, Collatos C. Equine degenerative myeloencephalopathy. Vet Clin North Am Equine Pract 1997;13:43-52.

    10. Lofstedt J. White muscle disease of foals. Vet Clin North Am Equine Pract 1997;13:169-185.

    11. McFarlane D, Dybdal N, Donaldson MT, et al. Nitration and increased alpha-synuclein expression associated with dopaminergic neurodegeneration in equine pituitary pars intermedia dysfunction. J Neuroendocrinol 2005;17:73-80.

    12. Yin C, Pettigrew A, Loftus JP, et al. Tissue concentrations of 4-HNE in the black walnut extract model of laminitis: indication of oxidant stress in affected laminae. Vet Immunol Immunopathol 2009;129(3-4):211-215.

    13. Vaala WE. Peripartum asphyxia. Vet Clin North Am Equine Pract 1994;10:187-218.

    14. Wilkins P. Disorders in foals. In: Reed S, Bayly W, Sellon D, eds. Equine Internal Medicine. 2nd ed. St. Louis, MO: Saunders; 2004:1381-1431.

    15. Voet D, Voet J. Introduction to metabolism. In: Voet D, Voet J, eds. Biochemistry. 2nd ed. New York: John Wiley & Sons; 1995:412-442.

    16. Marino P. Oxidant injury. In: Wingfield W, Raffe M, eds. The Veterinary ICU Book. Jackson Hole, WY: Teton NewMedia; 2002:24-39.

    17. McMichael M, Moore R. Ischemia-reperfusion injury pathophysiology, part I. J Vet Emerg Crit Care 2004;14:231-241.

    18. Van Metre DC, Callan RJ. Selenium and vitamin E. Vet Clin North Am Food Anim Pract 2001;17:373-402, vii-viii.

    19. Rohrmoser MM, Mayer G. Reactive oxygen species and glomerular injury. Kidney Blood Press Res 1996;19:263-269.

    20. Morrow JD. The isoprostanes: their quantification as an index of oxidant stress status in vivo. Drug Metab Rev 2000;32:377-385.

    21. Teoh NC, Farrell GC. Hepatic ischemia reperfusion injury: pathogenic mechanisms and basis for hepatoprotection. J Gastroenterol Hepatol 2003;18:891-902.

    22. Catala A. An overview of lipid peroxidation with emphasis in outer segments of photoreceptors and the chemiluminescence assay. Int J Biochem Cell Biol 2006;38:1482-1495.

    23. Cerqueira NF, Hussni CA, Yoshida WB. Pathophysiology of mesenteric ischemia/reperfusion: a review. Acta Cir Bras 2005;20:336-343.

    24. Cemeli E, Baumgartner A, Anderson D. Antioxidants and the Comet assay. Mutat Res 2009;681(1):51-67.

    25. Gayle JM, Blikslager AT, Jones SL. Role of neutrophils in intestinal mucosal injury. J Am Vet Med Assoc 2000;217:498-500.

    26. Vajdovich P. Free radicals and antioxidants in inflammatory processes and ischemia-reperfusion injury. Vet Clin North Am Small Anim Pract 2008;38:31-123, v.

    27. Voet D, Voet J. Glycolysis. In: Voet D, Voet J, eds. Biochemistry. 2nd ed. New York, NY: John Wiley & Sons; 1995:443-483.

    28. Allen S, Holm J. Lactate: physiology and clinical utility. J Vet Emerg Crit Care 2008;18:123-132.

    29. Murphy E, Steenbergen C. Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev 2008;88:581-609.

    30. Dong Z, Saikumar P, Weinberg JM, et al. Calcium in cell injury and death. Annu Rev Pathol 2006;1:405-434.

    31. Toledo-Pereyra LH, Lopez-Neblina F, Toledo AH. Protein kinases in organ ischemia and reperfusion. J Invest Surg 2008;21:215-226.

    32. Attuwaybi BO, Kozar RA, Moore-Olufemi SD, et al. Heme oxygenase-1 induction by hemin protects against gut ischemia/reperfusion injury. J Surg Res 2004;118:53-57.

    33. Schoenberg MH, Fredholm BB, Haglund U, et al. Studies on the oxygen radical mechanism involved in the small intestinal reperfusion damage. Acta Physiol Scand 1985;124:581-589.

    34. Sasaki M, Joh T. Oxidative stress and ischemia-reperfusion injury in gastrointestinal tract and antioxidant, protective agents. J Clin Biochem Nutr 2007;40:1-12.

    35. Mirza MH, Oliver JL, Seahorn TL, et al. Detection and comparison of nitric oxide in clinically normal horses and those with naturally acquired small intestinal strangulation obstruction. Can J Vet Res 1999;63:230-240.

    36. Li C, Jackson RM. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol 2002;282:C227-C241.

    37. Grosche A, Morton AJ, Polyak MM, et al. Detection of calprotectin and its correlation to the accumulation of neutrophils within equine large colon during ischaemia and reperfusion. Equine Vet J 2008;40:393-399.

    38. Moore RM, Bertone AL, Bailey MQ, et al. Neutrophil accumulation in the large colon of horses during low-flow ischemia and reperfusion. Am J Vet Res 1994;55:1454-1463.

    39. Rushing GD, Britt LD. Reperfusion injury after hemorrhage: a collective review. Ann Surg 2008;247:929-937.

    40. Dabareiner RM, Snyder JR, Sullins KE, et al. Evaluation of the microcirculation of the equine jejunum and ascending colon after ischemia and reperfusion. Am J Vet Res 1993;54:1683-1692.

    41. Seal JB, Gewertz BL. Vascular dysfunction in ischemia-reperfusion injury. Ann Vasc Surg 2005;19:572-584.

    42. Forsyth SF, Guilford WG. Ischaemia-reperfusion injury: a small animal perspective. Br Vet J 1995;151:281-298.

    43. Lopez-Neblina F, Toledo-Pereyra LH. Phosphoregulation of signal transduction pathways in ischemia and reperfusion. J Surg Res 2006;134:292-299.

    44. McMichael M. Ischemia-reperfusion injury: assessment and treatment, part II. J Vet Emerg Crit Care 2004;14:242-252.

    45. Ramachandran A, Jha S, Lefer DJ. Pathophysiology of myocardial reperfusion injury: the role of genetically engineered mouse models. Vet Pathol 2008;45:698-706.

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