Different doses of oxycodone on renal ischemia-reperfusion injury in rats

Abstract

Objective To evaluate the effects of different doses of oxycodone on renal ischemia-reperfusion (I/R) injury in rats. Methods Forty adult male Sprague-Dawley rats, weighing 220–300 g, aged 10–13 weeks, were randomly divided into 5 groups (n = 8 each) using a random number table: sham operation group (group S), group I/R, and low, medium and high doses of oxycodone groups (OL, OM and OH groups). After the rats underwent right nephrectomy, the renal I/R was induced by occlusion of the left renal artery and vein for 45 min with atraumatic microclips followed by 3 h reperfusion in I/R, OL, OM and OH groups.In group S, right nephrectomy was performed, and the left renal artery, vein and ureter were isolated without occluding blood flow.In OL, OM and OH groups, oxycodone 2, 4, and 6 mg/kg were infused intravenously, respectively, immediately after onset of ischemia.At 3 h of reperfusion, blood samples were taken from the abdominal aorta to determine the concentrations of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations.After blood sampling, the animals were sacrificed, and the left kidneys were removed for determination of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-8 and IL-10 contents (by using enzyme-linked immunosorbent assay), and malondialdehyde (MDA) content (by thiobarbituric acid method), and superoxide dismutase (SOD) activity (using xanthine oxidase method). Results Compared with group S, the serum BUN and Cr concentrations, and contents of TNF-α, IL-6, IL-8 and MDA in renal tissues were significantly increased, and the IL-10 content and SOD activity in renal tissues were decreased in the other four groups (P<0.05). Compared with group I/R, the serum BUN and Cr concentrations, and contents of TNF-α, IL-6, IL-8 and MDA in renal tissues were significantly decreased, and the IL-10 content and SOD activity in renal tissues were increased in OL, OM and OH groups (P<0.05). The serum BUN and Cr concentrations, and contents of TNF-α, IL-6, IL-8 and MDA in renal tissues were gradually decreased, and the IL-10 content and SOD activity in renal tissues were gradually increased with increasing dosage of oxycodone in OL, OM and OH groups (P< 0.05). Conclusion Oxycodone 2, 4, and 6 mg/kg can alleviate renal I/R injury in a dose-dependent manner in rats, and the mechanism is related to inhibition of inflammatory responses and oxidative stress response. Key words: Oxycodone; Reperfusion injury; Renal