Endothelial Permeability and 3-Nitrotyrosine in Major Burns

Abstract

In patients with extensive burns microvascular hyperpermeability occurs not only at the injured sites but also in regions distant from the injury. The mechanism of this burn oedema is still not completely understood, nor why it stops after 18-36 hours. However, there is increasing evidence that an overwhelming production of reactive oxygen and nitrogen species (ROS/RNS) plays an important role in this context. Our data document the generation of peroxynitrite (ONOO^-) by detection of its footprint 3-nitrotyrosine in thermally injured human skin. The immunohistological detection reveals the location of 3-nitrotyrosine at the endothelium and further adds to the hypothesis of oxidative/nitrosative stress. A promising therapeutic approach might be high-dose antioxidant treatment as the enhanced free radical production in burn trauma is paralleled by impaired antioxidant mechanisms. The most promising results for the reduction of oedema formation and decreased early resuscitation fluid volume are known for intravenous vitamin C treatment. This paper gives a short review of the literature on this topic.

Key words

Capillary leak - oedema - iNOS - reactive oxygen/nitrogen species - vitamin C

References

• 1 Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly.  Am J Physiol. 1996;  271 C1424-C1437
• 2 Bertin-Maghit M, Goudable J, Dalmas E. et al . Time course of oxidative stress after major burns.  Intensive Care Med. 2000;  26 800-803
• 3 Carter EA, Derojas-Walker T, Tamir S, Tannenbaum SR, Yu YM, Tompkins RG. Nitric oxide production is intensely and persistently increased in tissue by thermal injury.  Biochem J. 1994;  304 201-204
• 4 Cetinkale O, Belce A, Konukoglu D, Senyuva C, Gumustas MK, Tas T. Evaluation of lipid peroxidation and total antioxidant status in plasma of rats following thermal injury.  Burns. 1997;  23 114-116
• 5 Cuzzocrea S, Riley DP, Caputi AP, Salvemini D. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury.  Pharmacol Rev. 2001;  53 135-159
• 6 Frank J, Biesalski HK, Dominici S, Pompella A. The visualization of oxidant stress in tissues and isolated cells.  Histol Histopathol. 2000;  15 173-184
• 7 Frank J, Lambert C, Biesalski HK, Thews O, Vaupel P, Kelleher DK. Intensified oxidative and nitrosative stress following combined ALA-based photodynamic therapy and local hyperthermia in rat tumors.  Int J Cancer. 2003;  107 941-948
• 8 Greenacre SA, Ischiropoulos H. Tyrosine nitration: localisation, quantification, consequences for protein function and signal transduction.  Free Radic Res. 2001;  34 541-581
• 9 Greenacre SA, Rocha FA, Rawlingson A. et al . Protein nitration in cutaneous inflammation in the rat: essential role of inducible nitric oxide synthase and polymorphonuclear leukocytes.  Br J Pharmacol. 2002;  136 985-994
• 10 Guidarelli A, Fiorani M, Cantoni O. Enhancing effects of intracellular ascorbic acid on peroxynitrite-induced U937 cell death are mediated by mitochondrial events resulting in enhanced sensitivity to peroxynitrite-dependent inhibition of complex III and formation of hydrogen peroxide.  Biochem J. 2004;  378 959-966
• 11 Hattori Y, Nishigori C, Tanaka T. et al . 8-hydroxy-2′-deoxyguanosine is increased in epidermal cells of hairless mice after chronic ultraviolet B exposure.  J Invest Dermatol. 1996;  107 733-737
• 12 Horton JW. Free radicals and lipid peroxidation mediated injury in burn trauma: the role of antioxidant therapy.  Toxicology. 2003;  189 75-88
• 13 Horton JW, White DJ, Maass DL, Hybki DP, Haudek S, Giroir B. Antioxidant vitamin therapy alters burn trauma-mediated cardiac NF-kappaB activation and cardiomyocyte cytokine secretion.  J Trauma. 2001;  50 397-406
• 14 Huie RE, Padmaja S. The reaction of no with superoxide.  Free Radic Res Commun. 1993;  18 195-199
• 15 Inoue H, Ando K, Wakisaka N, Matsuzaki K, Aihara M, Kumagai N. Effects of nitric oxide synthase inhibitors on vascular hyperpermeability with thermal injury in mice.  Nitric Oxide. 2001;  5 334-342
• 16 Ischiropoulos H, Zhu L, Beckman JS. Peroxynitrite formation from macrophage-derived nitric oxide.  Arch Biochem Biophys. 1992;  298 446-451
• 17 Kurz CR, Kissner R, Nauser T, Perrin D, Koppenol WH. Rapid scavenging of peroxynitrous acid by monohydroascorbate.  Free Radic Biol Med. 2003;  35 1529-1537
• 18 LaLonde C, Nayak U, Hennigan J, Demling R. Antioxidants prevent the cellular deficit produced in response to burn injury.  J Burn Care Rehabil. 1996;  17 379-383
• 19 LaLonde C, Nayak U, Hennigan J, Demling RH. Excessive liver oxidant stress causes mortality in response to burn injury combined with endotoxin and is prevented with antioxidants.  J Burn Care Rehabil. 1997;  18 187-192
• 20 Latha B, Babu M. The involvement of free radicals in burn injury: a review.  Burns. 2001;  27 309-317
• 21 MacMicking JD, North RJ, LaCourse R, Mudgett JS, Shah SK, Nathan CF. Identification of nitric oxide synthase as a protective locus against tuberculosis.  Proc Natl Acad Sci USA. 1997;  94 5243-5248
• 22 Matsuda T, Tanaka H, Hanumadass M. et al . Effects of high-dose vitamin C administration on postburn microvascular fluid and protein flux.  J Burn Care Rehabil. 1992;  13 560-566
• 23 Matsuda T, Tanaka H, Reyes HM. et al . Antioxidant therapy using high dose vitamin C: reduction of postburn resuscitation fluid volume requirements.  World J Surg. 1995;  19 287-291
• 24 Matsuda T, Tanaka H, Williams S, Hanumadass M, Abcarian H, Reyes H. Reduced fluid volume requirement for resuscitation of third-degree burns with high-dose vitamin C.  J Burn Care Rehabil. 1991;  12 525-532
• 25 Matsuda T, Tanaka H, Yuasa H. et al . The effects of high-dose vitamin C therapy on postburn lipid peroxidation.  J Burn Care Rehabil. 1993;  14 624-629
• 26 Paulsen SM, Wurster SH, Nanney LB. Expression of inducible nitric oxide synthase in human burn wounds.  Wound Repair Regen. 1998;  6 142-148
• 27 Rawlingson A. Nitric oxide, inflammation and acute burn injury.  Burns. 2003;  29 631-640
• 28 Rawlingson A, Shendi K, Greenacre SA. et al . Functional significance of inducible nitric oxide synthase induction and protein nitration in the thermally injured cutaneous microvasculature.  Am J Pathol. 2003;  162 1373-1380
• 29 Ritter C, Andrades M, Guerreiro M. et al . Plasma oxidative parameters and mortality in patients with severe burn injury.  Intensive Care Med. 2003;  29 1380-1383
• 30 Saitoh D, Okada Y, Ookawara T. et al . Prevention of ongoing lipid peroxidation by wound excision and superoxide dismutase treatment in the burned rat.  Am J Emerg Med. 1994;  12 142-146
• 31 Salvemini D, Wang ZQ, Stern MK, Currie MG, Misko TP. Peroxynitrite decomposition catalysts: therapeutics for peroxynitrite-mediated pathology.  Proc Natl Acad Sci USA. 1998;  95 2659-2663
• 32 Sharma P, Raghavan SA, Saini R, Dikshit M. Ascorbate-mediated enhancement of reactive oxygen species generation from polymorphonuclear leukocytes: modulatory effect of nitric oxide.  J Leukoc Biol. 2004;  75 1070-1078
• 33 Soejima K, Traber LD, Schmalstieg FC. et al . Role of nitric oxide in vascular permeability after combined burns and smoke inhalation injury.  Am J Respir Crit Care Med. 2001;  163 745-752
• 34 Sozumi T. The role of nitric oxide in vascular permeability after a thermal injury.  Ann Plast Surg. 1997;  39 272-277
• 35 Szabo C, Salzman AL, Ischiropoulos H. Endotoxin triggers the expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in the rat aorta in vivo.  FEBS Lett. 1995;  363 235-238
• 36 Tanaka H, Broaderick P, Shimazaki S. et al . How long do we need to give antioxidant therapy during resuscitation when its administration is delayed for two hours?.  J Burn Care Rehabil. 1992;  13 567-572
• 37 Tanaka H, Hanumadass M, Matsuda H, Shimazaki S, Walter RJ, Matsuda T. Hemodynamic effects of delayed initiation of antioxidant therapy (beginning two hours after burn) in extensive third-degree burns.  J Burn Care Rehabil. 1995;  16 610-615
• 38 Tanaka H, Lund T, Wiig H. et al . High dose vitamin C counteracts the negative interstitial fluid hydrostatic pressure and early edema generation in thermally injured rats.  Burns. 1999;  25 569-574
• 39 Tanaka H, Matsuda T, Miyagantani Y, Yukioka T, Matsuda H, Shimazaki S. Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study.  Arch Surg. 2000;  135 326-331
• 40 Tanaka H, Matsuda H, Shimazaki S, Hanumadass M, Matsuda T. Reduced resuscitation fluid volume for second-degree burns with delayed initiation of ascorbic acid therapy.  Arch Surg. 1997;  132 158-161
• 41 Youn YK, LaLonde C, Demling R. Oxidants and the pathophysiology of burn and smoke inhalation injury.  Free Radic Biol Med. 1992;  12 409-415
• 42 Zellner PR, Lorenz S. Verbrennungskrankheiten. In: Lawin P (ed) Praxis der Intensivmedizin. Stuttgart: Thieme 1982

Correspondence