The effects of serium oxide against kidney damage caused by ibuprophen in rats with ureteral obstruction

THE EFFECTS OF SERIUM OXIDE AGAINST KIDNEY DAMAGE CAUSED BY IBUPROPHEN IN RATS WITH URETERAL OBSTRUCTION Aim: NSAIDs are indispensable agents in pain treatment. This situation causes limitations in the use of NSAIDs, which are completely removed from the body through the kidneys and known to have renal toxicity, in kidney diseases. The antioxidant cerium oxide (CeO2) can reduce the kidney toxicity due to NSAIDs in patients with kidney diseases. This study was designed to examine the effects of CeO2 on the kidney tissue of rats with unilateral ureter obstruction and renal failure following the use of ibuprofen. Materials and Methods: Thirty four-month-old male Wistar-albino rats weighing between 300-425 g were used in the study. The rats were kept at 20-21ºC temperature, 12 hours dark 12 hours light cycle and allowed to eat until 2 hours before the anesthesia. Rats were randomly divided into 5 groups, 6 in each group (Group C) Control, (Group UO) Ureter Obstruction, (Group UOI) Ureter Obstruction- Ibuprofen, (Group UOISO) Ureter Obstruction - Ibuprofen - Cerium Oxide, (Group UOSO) Ureter Obstruction-Cerium Oxide). Anesthesia was provided to rats by intramuscular injection of 50 mg/kg ketamine hydrocholoride (Ketalar® vial, Parke-Davis, USA) and 10 mg/kg xylazine hydrochloride (Alfazyne® , 2%, Ege Vet). The procedure was carried out under a heating lamp with the rats in the supine position. Under anesthesia, sham operation in control group and ureteal obstruction in other groups was performed with a low abdominal incision. The first dose of 0.5 mg/kg subcutaneous morphine sulfate was administered at the post-operative 0th hour and repeated every 8 hours until total 6 doses for postoperative analgesia. Serum BUN and creatinine values were measured after 3 weeks for the late period and were accepted as reference values. 3 weeks later after anesthesia euthanasia was carried out with intracardiac blood aspiration. Kidney tissues were removed delicately in order to preserve integrity and not be traumatized. Both kidney tissues were put into 10% formol for histopathological examination. Malondialdehyde (MDA), creatinine, BUN and NO parameters were measured. Glomerular vacuolization (GV), Tubular dilatation (TD), Vascular vacuolization and hypertrophy (VVH), Tubular cell degeneration and necrosis (TCDN), Bowman space dilatation (BSD), Tubular hyaline cylinders (THC), Lymphocyte infiltration (LI), Tubular cell shedding (TCS) were investigated in kidney tissues with and without ureter obstruction. Results: Histopathological evaluation under light microscopy revealed significantly less GV, THC and TCS in UOSO group compared to UOI group in right kidney (without obstruction). TD was observed significantly more in the left kidney tissue in UO and UOI groups compared to control group. No difference in terms of VVH, TCDN, BSD and LI was revealed between the groups. Histopathologically, GV, VVH and THC were found significantly less in the UOSO group than in the UOI group in the left kidney tissue (ureteral obstruction). TD, BSD, TCS and TCDN were signifiacantly more common in UO, UOI and UOISO compared to control group. THC was seen less in the UO and UOI groups than in control group. More LI was observed in the UOI group compared to the control group. While the MDA level was lower in the UOSO group compared to UOI group and NO enzyme activity was increased in UOI group. It was found that creatine and urea levels were similarly increased in obstruction groups. Conclusion: Our study is important as it is the first experimental study investigating the effect of CeO2 against kidney damage that with NSAID ibuprofen. We think that better results will be obtained in new CeO2 studies by differentiating groups in terms of age, sex and NSAIDs to examine biochemical parameters of oxidative damage with repeated exposure. Keywords: NSAID, kidney failure, ureter obstruction, cerium oxide