Pretreatment of parecoxib attenuates hepatic ischemia/reperfusion injury in rats

BMC Anesthesiology

Tao Zhang¹  Yi Ma²  Kang-Qing Xu¹  Wen-Qi Huang¹ 

[1] Department of Anesthesiology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China

[2] Organ transplantation center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China

关键词: Inflammation;    Cyclooxygenase-2;    Parecoxib;    Hepatic ischemia/reperfusion;   

Others  :  1233459
DOI  :  10.1186/s12871-015-0147-0

 received in 2015-05-05, accepted in 2015-11-11,  发布年份 2015

【 摘 要 】

Background

Previous studies showed that cyclooxygenase(COX) was involved in ischemia/reperfusion (I/R) injuries. Parecoxib, a selective inhibitor for COX −2, has been shown to have protective properties in reducing I/R injury in the heart, kidney and brain. The aim of this study was to investigate the effects of parecoxib on hepatic I/R and to explore the underlying mechanisms.

Methods

Fifty-two Sprague–Dawley rats were randomly divided into three groups: the sham-operation (Sham) group, the hepatic ischemia/reperfusion (I/R) group, and the parecoxib pretreated I/R (I/R + Pare) group. Partial warm ischemia was produced in the left and middle hepatic lobes of Sprague–Dawley rats for 60 min, followed by 6 h of reperfusion. Rats in the I/R + Pare group received parecoxib (10 mg/kg) intraperitoneally twice a day for three consecutive days prior to ischemia. Blood and tissue samples from the groups were collected 6 h after reperfusion, and a survival study was performed.

Results

Pretreatment with parecoxib prior to I/R insult significantly reduced I/R-induced elevations of aminotransferases, and significantly improved the histological status of the liver. Parecoxib significantly suppressed inflammatory cascades, as demonstrated by attenuations in TNF-α and IL-6. Parecoxib significantly inhibited iNOS and nitrotyrosine expression after I/R and significantly attenuated I/R-induced apoptosis. The 7-day survival rate was increased by pre-administration of parecoxib.

Conclusions

Administration of parecoxib prior to hepatic I/R attenuates hepatic injury through inhibition of inflammatory response and nitrosative stress.

【 授权许可】

   
2015 Zhang et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

Fig. 6.

【 参考文献 】

• [1]Montalvo-Jave EE, Escalante-Tattersfield T, Ortega-Salgado JA, Pina E, Geller DA. Factors in the pathophysiology of the liver ischemia-reperfusion injury. J Surg Res. 2008; 147:153-9.
• [2]Howard TK, Klintmalm GB, Cofer JB, Husberg BS, Goldstein RM, Gonwa TA. The influence of preservation injury on rejection in the hepatic transplant recipient. Transplantation. 1990; 49:103-107.
• [3]Kawai M, Harada N, Takeyama H, Okajima K. Neutrophil elastase contributes to the development of ischemia/reperfusion-induced liver injury by decreasing the production of insulin-like growth factor-I in rats. Transl Res. 2011; 155:294-304.
• [4]Hafez T, Moussa M, Nesim I, Baligh N, Davidson B, Abdul-Hadi A. The effect of intraportal prostaglandin E1 on adhesion molecule expression, inflammatory modulator function, and histology in canine hepatic ischemia/reperfusion injury. J Surg Res. 2007; 138(1):88-99.
• [5]Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Isakson P. Distribution of COX-1 and COX-2 in normal and inflamed tissues. Adv Exp Med Biol. 1997; 400A:167-170.
• [6]Morita I. Distinct functions of COX-1 and COX-2. Prostaglandins Other Lipid Mediat. 2002; 68–69:165-175.
• [7]Dupouy VM, Ferre PJ, Uro-Coste E, Lefebvre HP. Time course of COX-1 and COX-2 expression during ischemia-reperfusion in rat skeletal muscle. J Appl Physiol. 2006; 100:233-9.
• [8]Hiratsuka T, Futagami S, Tatsuguchi A, Suzuki K, Shinji Y, Kusunoki M et al.. COX-1 and COX-2 conversely promote and suppress ischemiareperfusion gastric injury in mice. Scand J Gastroenterol. 2005; 40:903-13.
• [9]Hamada T, Tsuchihashi S, Avanesyan A, Duarte S, Moore C, Busuttil RW et al.. Cyclooxygenase-2 deficiency enhances Th2 immune responses and impairs neutrophil recruitment in hepatic ischemia/ reperfusion injury. J Immunol. 2008; 180:1843-53.
• [10]Salloum FN, Hoke NN, Seropian IM, Varma A, Ownby ED, Houser JE et al.. Parecoxib inhibits apoptosis in acute myocardial infarction due to permanent coronary ligation but not due to ischemia-reperfusion. J Cardiovasc Pharmacol. 2009; 53:495-498.
• [11]Patel NS, Cuzzocrea S, Collino M, Chaterjee PK, Mazzon E, Britti D et al.. The role of cycloxygenase-2 in the rodent kidney following ischaemia/ reperfusion injury in vivo. Eur J Pharmacol. 2007; 562:148-154.
• [12]Kelsen J, Kjaer K, Chen G, Pedersen M, Røhl L, Frøkiaer J et al.. Parecoxib is neuroprotective in spontaneously hypertensive rats after transient middle cerebral artery occlusion: a divided treatment response? J Neuroinflammation. 2006; 3:31. BioMed Central Full Text
• [13]Heijnen BH, Straatsburg IH, Gouma DJ, van Gulik TM. Decrease in core liver temperature with 10 degrees C by in situ hypothermic perfusion under total hepatic vascular exclusion reduces liver ischemia and reperfusion injury during partial hepatectomy in pigs. Surgery. 2003; 134:806-17.
• [14]Moore C, Shen XD, Fondevila C, Gao F, Coito AJ. Blockade of fibronectin-alpha4beta1 adhesive interactions down-regulates cyclooxygenase-2 inducible nitric oxide synthase and prolongs recipient survival in a 24-hour model of cold hepatic ischemia-reperfusion injury. Transplant Proc. 2005; 37(4):1682-83.
• [15]Ito Y, Katagiri H, Ishii K, Kakita A, Hayashi I, Majima M. Effects of selective cyclooxygenase inhibitors on ischemia/reperfusion-induced hepatic microcirculatory dysfunction in mice. Eur Surg Res. 2003; 35:408-16.
• [16]Fu H, Chen H, Wang C, Xu H, Liu F, Guo M et al.. Flurbiprofen, a cyclooxygenase inhibitor, protects mice from hepatic ischemia/reperfusion injury by inhibiting GSK-3β signaling and mitochondrial permeability transition. Mol Med. 2012; 18:1128-35.
• [17]Iniguez MA, Punzon C, Fresno M. Induction of cyclooxygenase-2 on activated T lymphocytes: regulation of T cell activation by cyclooxygenase-2 inhibitors. J Immunol. 1999; 163(1):111-9.
• [18]Kim SF, Huri DA, Snyder SH. Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2. Science. 2005; 310(5756):1966-70.
• [19]Buvanendran A, Kroin JS, Berger RA, Hallab NJ, Saha C, Negrescu C et al.. Upregulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans. Anesthesiol. 2006; 104(3):403-10.
• [20]Feng Y, Ju H, Yang B, An H. Effects of a selective cycloxygenase-2 inhibitor on postoperative inflammatory reaction and pain after total knee replacement. J Pain. 2008; 9(1):45-52.
• [21]Colletti LM, Remick DG, Burtch GD, Kunkel SL, Strieter RM, Campbell DA. Role of tumor necrosis factor-a in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat. J Clin Invest. 1990; 85:1936-43.
• [22]Wustefeld T, Rakemann T, Kubicka S, Manns MP, Trautwein C. Hyperstimulation with interleukin 6 inhibits cell cycle progression after hepatectomy in mice. Hepatol. 2000; 32:514-22.
• [23]Wanner GA, Ertel W, Müller P, Höfer Y, Leiderer R, Menger MD et al.. Liver ischemia and reperfusion induces a systemic inflammatory response through Kupffer cell activation. Shock. 1996; 5(1):34-40.
• [24]Varadarajan R, Golden-Mason L, Young L, McLoughlin P, Nolan N, McEntee G et al.. Nitric oxide in early ischaemia reperfusion injury during human orthotopic liver transplantation. Transplantation. 2004; 78:250-6.
• [25]Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007; 87:315-424.