Effects of a single dose of parecoxib on the function, cell injury and inflammatory response of kidney of rats subjected to acute hemorrhage

INTRODUCTION: Parecoxib, the only selective COX-2 inhibitor available for parenteral use, has proven analgesic efficacy in the treatment of postoperative pain. However, adverse renal effects are not clear, especially in situations of renal hypoperfusion, such as hemorrhage and hypovolemia. Renal ischemia stimulates the production of inflammatory mediators, such as cytokines, responsible for the onset and progression of inflammation and renal injury. OBJECTIVE: The aim of this study was to evaluate whether pretreatment with a single dose of parecoxib affects the function, cell injury and inflammatory response of the kidney of rats subjected to acute intraoperative hemorrhage. METHODS: Forty-four adult Wistar rats anesthetized with sevoflurane were randomized into four groups (n = 11 animals per group): placebo/ without hemorrhage (Plac/NH); parecoxib/ without hemorrhage (Pcx/NH); placebo/ hemorrhage (Plac/H), and parecoxib/ hemorrhage (Pcx/H). They all received a single dose of intravenous parecoxib (20mg.kg-1 at 2 mL.kg-1) or placebo (isotonic saline 2mL.kg-1) according to group distribution. They also received solution of sodium para-aminohippurate (PAH) - 1 mg followed by 1 mg.h-1, and iothalamate sodium (IOT) - 0.5 mg followed by 0.25 mg.h-1, until the end of the experiment. Animals in groups with hemorrhage suffered bleeding corresponding to 30% of volemia (three-stage withdrawal of 10% with a 10 minute interval). Blood samples were collected to measure hematocrit and concentrations of PAH, IOT and serum cytokines (IL-1α, IL-1β, IL-6, IL-10 and TNF-α) thirty minutes after administration of bolus of parecoxib or placebo (Mi) and thirty minutes after the third time of bleeding (Mf). Bilateral nephrectomy was then performed, followed by sacrifice of the rats. Kidneys were longitudinally divided into two halves - one for histological analysis and the other to obtain the renal supernatant of proteins for determination of tissue cytokines (IL-1α, IL-1β, IL-6, IL-10 and TNF-α). RESULTS AND DISCUSSION: There was a decrease in mean arterial pressure and hematocrit in groups subjected to hemorrhage (Plac/H and Pcx/H) in Mf. Plac/H showed serum levels of IL-1α, IL-1β, IL-6, IL-10 and TNF-α higher than the other groups, suggesting that pretreatment with parecoxib reduced the inflammatory response in rats subjected to hemorrhage. Regarding tissue cytokines obtained in renal supernatant, there was no difference between groups. In both moments, Plac/NH > Plac/H and Pcx/H, and Pcx/NH > Plac/H with respect to PAH clearance. In relation to IOT clearance, Pcx/NH > Plac/H. There was no difference in filtration fraction between groups. Regarding renal vascular resistance, Plac/H > Plac/NH in both moments, and Mi> Mf in all groups. Thus, there was worse renal function in the group undergoing hemorrhage pretreated with placebo, with no significant improvement in these attributes in rats subjected to hemorrhage and treated with parecoxib. Plac/H showed higher percentage of tubular dilatation and degeneration, with no difference between groups in the degree of vascular congestion and ectasia. CONCLUSION: Pretreatment with a single dose of parecoxib reduced the inflammatory response and renal injury without altering renal function in rats undergoing acute hemorrhage.