Burn injuries result in the release of proinflammatory mediators causing both local and systemic inflammation. Multiple organ dysfunctions secondary to systemic inflammation after severe burn contribute to adverse outcome, with the lungs being the first organ to fail. In this study, we evaluate the anti-inflammatory effects of Parecoxib, a parenteral COX-2 inhibitor, in a delayed fluid resuscitation burned rat model. Anaesthetized Sprague Dawley rats were inflicted with 45% total body surface area full-thickness scald burns and subsequently subjected to delayed resuscitation with Hartmann’s solution. Parecoxib (0.1, 1.0, and 10？mg/kg) was delivered intramuscularly 20？min after injury followed by 12？h interval and the rats were sacrificed at 6？h, 24？h, and 48？h. Burn rats developed elevated blood cytokines, transaminase, creatinine, and increased lung MPO levels. Animals treated with 1？mg/kg Parecoxib showed significantly reduced plasma level of CINC-1, IL-6, PGEM, and lung MPO. Treatment of 1？mg/kg Parecoxib is shown to mitigate systemic and lung inflammation without significantly affecting other organs. At present, no specific therapeutic agent is available to attenuate the systemic inflammatory response secondary to burn injury. The results suggest that Parecoxib may have the potential to be used both as an analgesic and ameliorate the effects of lung injury following burn. 1. Introduction Burn injury results in increased microvascular permeability leading to edema formation due to the loss in plasma fluid to the interstitial space [1]. Timely and early resuscitation of burn shock is effective in restoring normal tissue perfusion. However, severe burn victims are in pain, uncooperative, and unable to seek help that may delay evacuation. When resuscitation is delayed, recovery can be complicated by multiple end-organ failure due to systemic inflammation after severe burn and systemic inflammatory response syndrome (SIRS) has remained the primary cause of death in critically injured patients, with acute respiratory distress syndrome (ARDS) as the leading cause [2, 3]. An early management of burn injury is essential for the good prognosis of burn patient. It has been reported that early control of inflammation after burn improves pulmonary function and survival [4, 5]. Consistent in these findings, Cyclooxygenase-2 (COX-2) has been shown to mediate inflammatory process through prostaglandins release after burn injury and inhibition of COX-2 attenuated proinflammatory cytokines, chemokines, and acute lung injury in burn-injured mice [6–8]. Parecoxib, a
References
[1]
R. H. Demling, “The burn edema process: current concepts,” Journal of Burn Care and Rehabilitation, vol. 26, no. 3, pp. 207–227, 2005.
[2]
R. H. Turnage, F. Nwariaku, J. Murphy, C. Schulman, K. Wright, and H. Yin, “Mechanisms of pulmonary microvascular dysfunction during severe burn injury,” World Journal of Surgery, vol. 26, no. 7, pp. 848–853, 2002.
[3]
D. R. Dancey, J. Hayes, M. Gomez et al., “ARDS in patients with thermal injury,” Intensive Care Medicine, vol. 25, no. 11, pp. 1231–1236, 1999.
[4]
K. Ipaktchi, A. Mattar, A. D. Niederbichler et al., “Attenuating burn wound inflammation improves pulmonary function and survival in a burn-pneumonia model,” Critical Care Medicine, vol. 35, no. 9, pp. 2139–2144, 2007.
[5]
T. J. Murphy, H. M. Paterson, S. Kriynovich et al., “Linking the “two-hit” response following injury to enhanced TLR4 reactivity,” Journal of Leukocyte Biology, vol. 77, no. 1, pp. 16–23, 2005.
[6]
L.-K. He, L. H. Liu, E. Hahn, and R. L. Gamelli, “The expression of cyclooxygenase and the production of prostaglandin E2 in neutrophils after burn injury and infection,” Journal of Burn Care and Rehabilitation, vol. 22, no. 1, pp. 58–64, 2001.
[7]
G. A. FitzGerald, “COX-2 and beyond: approaches to prostaglandin inhibition in human disease,” Nature Reviews Drug Discovery, vol. 2, no. 11, pp. 879–890, 2003.
[8]
T. A. Wilgus, M. S. Ross, M. L. Parrett, and T. M. Oberyszyn, “Topical application of a selective cyclooxygenase inhibitor suppresses UVB mediated cutaneous inflammation,” Prostaglandins and Other Lipid Mediators, vol. 62, no. 4, pp. 367–384, 2000.
[9]
S. W. S. Sio, S. F. Ang, J. Lu, S. Moochhala, and M. Bhatia, “Substance p upregulates cyclooxygenase-2 and prostaglandin E metabolite by activating ERK1/2 and NF-κB in a mouse model of burn-induced remote Acute lung injury,” Journal of Immunology, vol. 185, no. 10, pp. 6265–6276, 2010.
[10]
Y. Ozaki-Okayama, K. Matsumura, T. Ibuki et al., “Burn injury enhances brain prostaglandin E2 production through induction of cyclooxygenase-2 and microsomal prostaglandin E synthase in cerebral vascular endothelial cells in rats,” Critical Care Medicine, vol. 32, no. 3, pp. 795–800, 2004.
[11]
J. Kelsen, K. Kj？r, G. Chen et al., “Parecoxib is neuroprotective in spontaneously hypertensive rats after transient middle cerebral artery occlusion: a divided treatment response?” Journal of Neuroinflammation, vol. 3, article 31, 2006.
[12]
H. L. Walker and A. D. Mason Jr., “A standard animal burn,” Journal of Trauma, vol. 8, no. 6, pp. 1049–1051, 1968.
[13]
N. Aikawa, Y. Shinozawa, and K. Ishibiki, “Clinical analysis of multiple organ failure in burned patients,” Burns, vol. 13, no. 2, pp. 103–109, 1987.
[14]
H. Baskaran, M. L. Yarmush, and F. Berthiaume, “Dynamics of tissue neutrophil sequestration after cutaneous burns in rats,” Journal of Surgical Research, vol. 93, no. 1, pp. 88–96, 2000.
[15]
A. J. Singer, E. Wang, B. R. Taira, N. Steinhauff, J. Rooney, and T. Zimmerman, “Controlled mild hypothermia prolongs survival in a rat model of large scald burns,” Academic Emergency Medicine, vol. 18, no. 3, pp. 287–291, 2011.
[16]
J.-P. Zhang, X. Ying, W.-Y. Liang et al., “Apoptosis in cardiac myocytes during the early stage after severe burn,” The Journal of Trauma, vol. 65, no. 2, pp. 401–408, 2008.
[17]
R. M. Green and S. Flamm, “AGA technical review on the evaluation of liver chemistry tests,” Gastroenterology, vol. 123, no. 4, pp. 1367–1384, 2002.
[18]
D. S. Pratt and M. M. Kaplan, “Evaluation of abnormal liver-enzyme results in asymptomatic patients,” The New England Journal of Medicine, vol. 342, no. 17, pp. 1266–1271, 2000.
[19]
P. B. Watkins, N. Kaplowitz, J. T. Slattery et al., “Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial,” Journal of the American Medical Association, vol. 296, no. 1, pp. 87–93, 2006.
[20]
V. G. Athyros, K. Tziomalos, T. D. Gossios et al., “Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis,” The Lancet, vol. 376, no. 9756, pp. 1916–1922, 2010.
[21]
U. A. Boelsterli, H. J. Zimmerman, and A. Kretz-Rommel, “Idiosyncratic liver toxicity of nonsteroidal antiinflammatory drugs: molecular mechanisms and pathology,” Critical Reviews in Toxicology, vol. 25, no. 3, pp. 207–235, 1995.
[22]
D. Bjorkman, “Nonsteroidal anti-inflammatory drug-associated toxicity of the liver, lower gastrointestinal tract, and esophagus,” The American Journal of Medicine, vol. 105, no. 5, pp. 17S–21S, 1998.
[23]
G. G. Gauglitz, J. Song, D. N. Herndon et al., “Characterization of the inflammatory response during acute and post-acute phases after severe burn,” Shock, vol. 30, no. 5, pp. 503–507, 2008.
[24]
L.-W. Chen, B. Hwang, W.-J. Chang, J.-S. Wang, J.-S. Chen, and C.-M. Hsu, “Inducible nitric oxide synthase inhibitor reverses exacerbating effects of hypertonic saline on lung injury in burn,” Shock, vol. 22, no. 5, pp. 472–477, 2004.
[25]
S. ？. Iseri, Y. Ersoy, N. Gedik, F. Ercan, and I. Alican, “Protective role of adrenomedullin in burn-induced remote organ damage in the rat,” Regulatory Peptides, vol. 146, no. 1–3, pp. 99–105, 2008.
[26]
C. R. Baxter, “Management of fluid volume and electrolyte changes in the early postburn period,” Geriatrics, vol. 30, no. 11, pp. 57–62, 1975.
[27]
D. G. Greenhalgh and G. D. Warden, “The importance of intra-abdominal pressure measurements in burned children,” Journal of Trauma, vol. 36, no. 5, pp. 685–690, 1994.
[28]
B. A. Latenser, A. Kowal-Vern, D. Kimball, A. Chakrin, and N. Dujovny, “A pilot study comparing percutaneous decompression with decompressive laparotomy for acute Abdominal Compartment Syndrome in thermal injury,” Journal of Burn Care and Rehabilitation, vol. 23, no. 3, pp. 190–195, 2002.
[29]
K. G. Hobson, K. M. Young, A. Ciraulo, T. L. Palmieri, and D. G. Greenhalgh, “Release of abdominal compartment syndrome improves survival in patients with burn injury,” Journal of Trauma: Injury, Infection and Critical Care, vol. 53, no. 6, pp. 1129–1133, 2002.
[30]
J. Oda, K. Yamashita, T. Inoue et al., “Resuscitation fluid volume and abdominal compartment syndrome in patients with major burns,” Burns, vol. 32, no. 2, pp. 151–154, 2006.
[31]
C. C. Finnerty, R. Przkora, D. N. Herndon, and M. G. Jeschke, “Cytokine expression profile over time in burned mice,” Cytokine, vol. 45, no. 1, pp. 20–25, 2009.
[32]
M. Kataranovski, Z. Magi？, and N. Pejnovi？, “Early inflammatory cytokine and acute phase protein response under the stress of thermal injury in rats,” Physiological Research, vol. 48, no. 6, pp. 473–482, 1999.
[33]
G. G. Gauglitz, J. Song, D. N. Herndon et al., “Characterization of the inflammatory response during acute and post-acute phases after severe burn,” Shock, vol. 30, no. 5, pp. 503–507, 2008.
[34]
J. L. Rodriguez, C. G. Miller, W. L. Garner et al., “Correlation of the local and systemic cytokine response with clinical outcome following thermal injury,” Journal of Trauma, vol. 34, no. 5, pp. 684–696, 1993.
[35]
M. H. G. Gehling, T. Luesebrink, P. J. Kulka, and M. Tryba, “The effective duration of analgesia after intrathecal morphine in patients without additional opioid analgesia: a randomized double-blind multicentre study on orthopaedic patients,” European Journal of Anaesthesiology, vol. 26, no. 8, pp. 683–688, 2009.
[36]
K. S. Luscombe, N. J. McDonnell, N. A. Muchatuta, M. J. Paech, and E. A. Nathan, “A randomised comparison of parecoxib versus placebo for pain management following minor day stay gynaecological surgery,” Anaesthesia and Intensive Care, vol. 38, no. 1, pp. 141–148, 2010.
[37]
R. Lloyd, S. Derry, R. A. Moore, and H. J. McQuay, “Intravenous or intramuscular parecoxib for acute postoperative pain in adults,” Cochrane Database of Systematic Reviews, no. 2, Article ID CD004771, 2009.
[38]
P. Piper and J. Vane, “The release of prostaglandins from lung and other tissues,” Annals of the New York Academy of Sciences, vol. 180, pp. 363–385, 1971.
[39]
A. Whelton, “Renal and related cardiovascular effects of conventional and COX-2-specific NSAIDs and non-NSAID analgesics,” American Journal of Therapeutics, vol. 7, no. 2, pp. 63–74, 2000.
[40]
R. C. Harris, J. A. McKanna, Y. Akai, H. R. Jacobson, R. N. Dubois, and M. D. Breyer, “Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction,” Journal of Clinical Investigation, vol. 94, no. 6, pp. 2504–2510, 1994.
[41]
T. Mori, A. W. Cowley Jr., and S. Ito, “Molecular mechanisms and therapeutic strategies of chronic renal injury: physiological role of angiotensin II-induced oxidative stress in renal medulla,” Journal of Pharmacological Sciences, vol. 100, no. 1, pp. 2–8, 2006.
[42]
M. D. Murray and D. C. Brater, “Renal toxicity of the nonsteroidal anti-inflammatory drugs,” Annual Review of Pharmacology and Toxicology, vol. 33, pp. 435–465, 1993.
[43]
D. C. Brater, “Effects of nonsteroidal anti-inflammatory drugs on renal function: focus on cyclooxygenase -2-selective inhibition,” American Journal of Medicine, vol. 107, no. 6, pp. 65S–70S, 1999.
[44]
G. Arturson, “Pathophysiology of the burn wound and pharmacological treatment. The Rudi Hermans Lecture, 1995,” Burns, vol. 22, no. 4, pp. 255–274, 1996.
[45]
M. Bhatia and S. Moochhala, “Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome,” Journal of Pathology, vol. 202, no. 2, pp. 145–156, 2004.
[46]
P. Dahiya, “Burns as a model of SIRS,” Frontiers in Bioscience, vol. 14, no. 13, pp. 4962–4967, 2009.
