Effects of a Single Dose of Parecoxib on Inflammatory Response and Ischemic Tubular Injury Caused by Hemorrhagic Shock in Rats.

Mariana Takaku,Andre Carnevali Da Silva,Nathalie Izumi Iritsu,Pedro Thadeu Galvao Vianna,Yara Marcondes Machado Castiglia

doi:10.1155/2018/8375746

Abstract

Parecoxib, a selective COX-2 inhibitor, is used to improve analgesia in postoperative procedures. Here we evaluated whether pretreatment with a single dose of parecoxib affects the function, cell injury, and inflammatory response of the kidney of rats subjected to acute hemorrhage. Inflammatory response was determined according to serum and renal tissue cytokine levels (IL-1α, IL-1β, IL-6, IL-10, and TNF-α). Forty-four adult Wistar rats anesthetized with sevoflurane were randomized into four groups: placebo/no hemorrhage (Plc/NH); parecoxib/no hemorrhage (Pcx/NH); placebo/hemorrhage (Plc/H); and parecoxib/hemorrhage (Pcx/H). Pcx groups received a single dose of intravenous parecoxib while Plc groups received a single dose of placebo (isotonic saline). Animals in hemorrhage groups underwent bleeding of 30% of blood volume. Renal function and renal histology were then evaluated. Plc/H showed the highest serum levels of cytokines, suggesting that pretreatment with parecoxib reduced the inflammatory response in rats subjected to hemorrhage. No difference in tissue cytokine levels between groups was observed. Plc/H showed higher percentage of tubular dilation and degeneration, indicating that parecoxib inhibited tubular injury resulting from renal hypoperfusion. Our findings indicate that pretreatment with a single dose of parecoxib reduced the inflammatory response and tubular renal injury without altering renal function in rats undergoing acute hemorrhage.

Highlights

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed therapeutic agents for reducing acute pain and are often used to improve analgesia and reduce opioid consumption, accelerating recovery after surgery [1,2,3].Conventional NSAIDs block both cyclooxygenase (COX) enzyme isoforms, COX-1 and COX-2
The levels of proinflammatory cytokines IL-1α, IL-1β, IL-6, and TNF-α are higher in ischemic renal injury and these cytokines are involved in different mechanisms of renal tissue injury
The aim of this study was to evaluate whether pretreatment with a single dose of parecoxib affects renal function, renal tissue injury, and inflammatory response in rats submitted to acute hemorrhage

Summary

Introduction

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed therapeutic agents for reducing acute pain and are often used to improve analgesia and reduce opioid consumption, accelerating recovery after surgery [1,2,3].Conventional NSAIDs block both cyclooxygenase (COX) enzyme isoforms, COX-1 and COX-2. Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed therapeutic agents for reducing acute pain and are often used to improve analgesia and reduce opioid consumption, accelerating recovery after surgery [1,2,3]. Inflammation plays a major role in the pathophysiology of acute ischemic renal injury [8, 9]. The renal ischemia promotes endothelial and tubular cell injury, release of inflammatory mediators, such as cytokines and chemokines, and leukocyte infiltration into the renal tissue [9]. IL-10 is an anti-inflammatory cytokine that inhibits cytotoxicity and inflammation pathways and protects from ischemic renal injury [8,9,10,11]

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