%0 Journal Article
%T Parecoxib Reduces Systemic Inflammation and Acute Lung Injury in Burned Animals with Delayed Fluid Resuscitation
%A Si Jack Chong
%A Yong Chiat Wong
%A Jian Wu
%A Mui Hong Tan
%A Jia Lu
%A Shabbir M. Moochhala
%J International Journal of Inflammation
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/972645
%X 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¨C8]. Parecoxib, a
%U http://www.hindawi.com/journals/iji/2014/972645/