Dexmedetomidine on renal ischemia-reperfusion injury in rats: assessment by means of NGAL and histology (original) (raw)
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Brazilian Journal of Anesthesiology (English Edition), 2014
Background and objectives: We investigated the effect of dexmedetomidine on ischemic renal failure in rats. Methods: In the present study, 26 male adult Wistar albino rats weighting 230-300 g were randomly separated into four groups: sham-operated (n = 5), ischemia reperfusion (IR) (IR group, n = 7), IR/reperfusion treatment with dexmedetomidine (Dex. R group, n = 7) and IR/preischemic treatment with dexmedetomidine (Dex. I group, n = 7). In the first group, sham operation was achieved and renal clamps were not applied. For the IR group, renal ischemia was induced by occlusion of the bilateral renal arteries and veins for 60 min followed by reperfusion for 24 h. For the Dex. R and Dex. I groups, the same surgical procedure as in the IR group was performed, and dexmedetomidine (100 mcg/kg intraperitoneal) was administrated at the 5th min after reperfusion and before ischemia. At the end of reperfusion, blood samples were drawn, the rats were sacrificed, and the left kidney was processed for histopathology. Results: The blood urea nitrogen (BUN) levels in groups Dex. R and Dex. I were significantly lower than in the IR group (p = 0.015, p = 0.043), although urine flow was significantly higher in group Dex. R (p = 0.003). The renal histopathological score in the IR group was significantly higher than in the other groups. There was no significant difference between the Dex. R and Dex. I groups.
Drug Design, Development and Therapy, 2017
Background: Ischemia-reperfusion (I/R) injury is a common cause of patient morbidity and mortality in the perioperative period. Patients undergoing long-lasting, abdominal, and urogenital surgeries with risk factors such as advanced age, peripheral artery disease, diabetes mellitus, renovascular disease, and congestive heart failure are candidates for acute kidney injury (AKI) due to impaired renal perfusion and decreased functional renal reserve. Pharmacological agents with multiple functions and anti-oxidative and anti-inflammation properties may be promising preventative strategies for AKI. Recently, dexmedetomidine (dex) has been postulated to have renoprotective effects. Objectives: We aimed to investigate the protective effects of an intravenous anesthetic remifentanil in renal I/R injury in the rat in comparison with dex. Materials and methods: A total of 30 Sprague Dawley adult rats were randomly assigned into five groups: the control group (group C, n=6), the sham group (group Sh, n=6, saline-infused rats without I/R injury), the saline group (group S, n=6, saline-infused rats with I/R injury), the remifentanil-treated group (group REM, n=6), and the dexmedetomidine-treated group (group DEX, n=6). The infusions (saline, remifentanil, and dex) were started after anesthesia induction and right nephrectomy and continued until the end of the surgical procedure. In I/R injury groups, the left renal artery and vein were occluded together by a clamp for 30 minutes and reperfusion lasted for 30 minutes. The rats were sacrificed after reperfusion, and the left kidney tissue was harvested. Blood samples were drawn from all animals to evaluate plasma neutrophil gelatinase-associated lipocalin (NGAL) at the beginning, 15 minutes after ischemia, 15 minutes after reperfusion, and 6 hours after the surgical procedure (T0, T1, T2, and T3, respectively). Results: The plasma NGAL levels exhibited increase at T1, T2, and T3 compared to the levels at T0 in group S (P,0.05). In group REM, there was a significant increase in plasma NGAL levels at T3 in comparison to those at T0, T1, and T2. The plasma NGAL levels at T2 in group S were significantly higher than those at T2 in group DEX (P,0.05). The groups S and REM showed significantly higher plasma NGAL levels at T3 compared to those at T0 (P,0.05). Upon histological examination, there was no difference among the study groups when left kidneys were evaluated (P.0.05). Conclusion: The NGAL levels and histopathological findings reflected protection by dex against renal I/R injury. However, the same exact results could not be mentioned for remifentanil depending on our study results.
Renal failure, 2015
Dexmedetomidine (dex) is a potent, highly selective and specific α2-adrenoreceptor agonist. This experimental study was designed to investigate protective and therapeutic effect of two different doses of dex, on kidney damage induced by ischemia-reperfusion (I/R) in rats. Male Sprague-Dawley rats were divided into four groups, each including 10 animals: control group, ischemia-reperfusion (I/R) group; treated groups with 10 μg/kg of dex and 100 μg/kg of dex. After removing right kidney of the rats, the left kidney has performed ischemia during 40 min and reperfusion in the following 3 h. The histopathological findings, and also tissue superoxide dismutase (SOD) and catalase (CAT) enzyme activity, malondialdehyde (MDA), glutathione (GSH), serum blood urea nitrogen (BUN), creatinine (Cre) and tumor necrosis factor-alpha (TNF-α) levels were determined. In the I/R group, compared to the control group, levels of BUN, Cre and kidney tissue MDA have increased significantly, SOD, CAT enzyme...
Drug Design, Development and Therapy, 2017
Background: Ischemia-reperfusion (I/R) injury is a common cause of patient morbidity and mortality in the perioperative period. Patients undergoing long-lasting, abdominal, and urogenital surgeries with risk factors such as advanced age, peripheral artery disease, diabetes mellitus, renovascular disease, and congestive heart failure are candidates for acute kidney injury (AKI) due to impaired renal perfusion and decreased functional renal reserve. Pharmacological agents with multiple functions and anti-oxidative and anti-inflammation properties may be promising preventative strategies for AKI. Recently, dexmedetomidine (dex) has been postulated to have renoprotective effects. Objectives: We aimed to investigate the protective effects of an intravenous anesthetic remifentanil in renal I/R injury in the rat in comparison with dex. Materials and methods: A total of 30 Sprague Dawley adult rats were randomly assigned into five groups: the control group (group C, n=6), the sham group (group Sh, n=6, saline-infused rats without I/R injury), the saline group (group S, n=6, saline-infused rats with I/R injury), the remifentanil-treated group (group REM, n=6), and the dexmedetomidine-treated group (group DEX, n=6). The infusions (saline, remifentanil, and dex) were started after anesthesia induction and right nephrectomy and continued until the end of the surgical procedure. In I/R injury groups, the left renal artery and vein were occluded together by a clamp for 30 minutes and reperfusion lasted for 30 minutes. The rats were sacrificed after reperfusion, and the left kidney tissue was harvested. Blood samples were drawn from all animals to evaluate plasma neutrophil gelatinase-associated lipocalin (NGAL) at the beginning, 15 minutes after ischemia, 15 minutes after reperfusion, and 6 hours after the surgical procedure (T0, T1, T2, and T3, respectively). Results: The plasma NGAL levels exhibited increase at T1, T2, and T3 compared to the levels at T0 in group S (P,0.05). In group REM, there was a significant increase in plasma NGAL levels at T3 in comparison to those at T0, T1, and T2. The plasma NGAL levels at T2 in group S were significantly higher than those at T2 in group DEX (P,0.05). The groups S and REM showed significantly higher plasma NGAL levels at T3 compared to those at T0 (P,0.05). Upon histological examination, there was no difference among the study groups when left kidneys were evaluated (P.0.05). Conclusion: The NGAL levels and histopathological findings reflected protection by dex against renal I/R injury. However, the same exact results could not be mentioned for remifentanil depending on our study results.
Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES, 2017
The aim of this study was to evaluate the effects of remote ischemic preconditioning (RIPC) and dexmedetomidine as pharmacological conditioning in a rat renal ischemia/reperfusion (IR) injury model. Total of 28 male Wistar Albino rats weighing 250 to 300 g were divided into 4 equal groups. Group I (Sham; n=7): Laparotomy and renal pedicle dissection were performed, and the rats were observed under anesthesia without any intervention. Group II (IR; n=7): Following laparotomy and 45 minutes of left renal pedicle occlusion, 4 hours of reperfusion was performed. Group III (IR+D; n=7): Following laparotomy and ischemia, dexmedetomidine was administrated intraperitoneally (100 µg/kg) at fifth minute of reperfusion. Group IV (RIPC+IR; n=7): Under anesthesia, 3 cycles of ischemic preconditioning were applied to the left hind leg, and after 5 minutes, renal IR was performed. All rats were sacrificed after the left kidney was processed for conventional histomorphology. Total histomorphologica...
Libyan Journal of Medicine, 2017
Aim: The aim of this study was to investigate whether dexmedetomidineadministered before ischemiahas protective effects against lower extremity ischemia reperfusion injury that induced by clamping and subsequent declamping of infra-renal abdominal aorta in streptozotocin-induced diabetic rats. Material and Methods: After obtaining ethical committee approval, four study groups each containing six rats were created (Control (Group C), diabetes-control (Group DM-C), diabetes I/R (Group DM-I/R), and diabetes-I/R-dexmedetomidine (Group DM-I/R-D). In diabetes groups, single-dose (55 mg/kg) streptozotocin was administered intraperitoneally. Rats with a blood glucose level above 250 mg/dl at the 72nd hour were accepted as diabetic. At the end of four weeks, laparotomy was performed in all rats. Nothing else was done in Group C and DM-C. In Group DM-I/R, ischemia reperfusion was produced via two-hour periods of clamping and subsequent declamping of infra-renal abdominal aorta. In Group DM-I/R-D, 100 μg/kg dexmedetomidine was administered intraperitoneally 30 minutes before ischemia period. At the end of reperfusion, period biochemical and histopathological evaluation of renal tissue specimen were performed. Results: Thiobarbituric acid reactive substance (TBARS), Superoxide dismutase (SOD), Nitric oxide synthase (NOS), Catalase (CAT) and Glutathion S transferase (GST) levels were found significantly higher in Group DM-I/R when compared with Group C and Group DM-C. In the dexmedetomidine-treated group, TBARS, NOS, CAT, and GST levels were significantly lower than those measured in the Group D-I/R. In histopathological evaluation, glomerular vacuolization (GV), tubular dilatation (TD), vascular vacuolization and hypertrophy (VVH), tubular cell degeneration and necrosis (TCDN), tubular hyaline cylinder (THC), leucocyte infiltration (LI), and tubular cell spillage (TCS) in Group DM-I/R were significantly increased when compared with the control group. Also, GV, VVH, and THC levels in the dexmedetomidinetreated group (Group DM-I/R-D) were found significantly decreased when compared with the Group DM-I/R. Conclusion: We found that dexmedetomidine − 100 μg/kg intraperitoneallyadministered 30 minutes before ischemia in diabetic rats ameliorates lipid peroxidation, oxidative stress, and I-R-related renal injury. We suggest that dexmedetomidine administration in diabetic rats before I/R has renoprotective effects.
Brazilian Journal of Anesthesiology, 2014
Background and objectives: The aim of this study was to evaluate the effects of remote ischemic preconditioning by brief ischemia of unilateral hind limb when combined with dexmedetomidine on renal ischemia-reperfusion injury by histopathology and active caspase-3 immunoreactivity in rats. Methods: 28 Wistar albino male rats were divided into 4 groups. Group I (Sham, n = 7): Laparotomy and renal pedicle dissection were performed at 65th minute of anesthesia and the rats were observed under anesthesia for 130 min. Group II (ischemia-reperfusion, n = 7): At 65th minute of anesthesia bilateral renal pedicles were clamped. After 60 min ischemia 24 h of reperfusion was performed. Group III (ischemia-reperfusion + dexmedetomidine, n = 7): At the fifth minute of reperfusion (100 g/kg intra-peritoneal) dexmedetomidine was administered with ischemia-reperfusion group. Reperfusion lasted 24 h. Group IV (ischemia-reperfusion + remote ischemic preconditioning + dexmedetomidine, n = 7): After laparotomy, three cycles of ischemic preconditioning (10 min ischemia and 10 min reperfusion) were applied to the left hind limb and after 5 min with group III. Results: Histopathological injury scores and active caspase-3 immunoreactivity were significantly lower in the Sham group compared to the other groups. Histopathological injury scores in groups III and IV were significantly lower than group II (p = 0.03 and p = 0.05). Active caspase-3 immunoreactivity was significantly lower in the group IV than group II (p = 0.01) and there was no significant difference between group II and group III (p = 0.06).
Dexmedetomidine and S (+)-ketamine in ischemia and reperfusion injury in the rat kidney
2011
To investigate blood creatinine and renal histology in rats anesthetized with S(+)-ketamine (keta) or dexmedetomidine (dex) and submitted to kidney ischemia/reperfusion injury (IRI). Methods: Under intraperitoneal (ip) S(+)-ketamine, 20 male Wistar rats were divided into two groups (n=10): maintenance with iv S(+)-ketamine or dex (keta and dex groups), and submitted to right (R) nephrectomy and left (L) renal artery clamping for 45 min. Blood creatinine was measured before ischemia (T1) and 48h after reperfusion (T2), when L nephrectomy was performed. Histological analysis was performed in all kidneys. Results: Blood creatinine was significantly higher at T2 in both groups, but dex group results were lower than those of keta group. Histological changes: between groups, R kidneys did not differ; there were significant high scores for vascular dilation: keta L kidneys; for vascular congestion, tubular dilation, and necrosis: L kidneys from both groups; for tubular degeneration: keta R kidneys. Conclusion: S(+)-ketamine plus IRI were aggressive to rat kidneys, according to histological changes, and dexmedetomidine may have not totally protected the kidneys from these injuries, despite the better results of blood creatinine.
Annals of Vascular Surgery, 2012
Background: Ischemia/reperfusion (I/R) injury of tissues is a common problem that cardiovascular surgeons are faced with. Suppression of inflammation, which plays an important role in the pathogenesis of I/R injury, may reduce this damage. The aim of this study is to investigate the protective effects of methylprednisolone (MP)da potent anti-inflammatory agentdand pheniramine maleate (FM)dan antihistamine that also has some anti-inflammatory effectsdon reperfusion injury of kidneys developing after ischemia of the left lower extremity of rats. Methods: Twenty-eight randomly selected male SpragueeDawley rats weighing 320 to 370 g were divided into four groups, each consisting of seven rats. Group 1 was the control group. Group 2 was the sham group. Rats in group 3 were subjected to I/R and given FM, and rats in group 4 were subjected to I/R and given MP. A tourniquet was applied at the level of the left groin to subjects in group 2 after induction of anesthesia. One hour of ischemia was performed, and no drug was administered. In group 3, half of a total dose of 10 mg/kg FM was administered before ischemia, and the remaining half was given intraperitoneally before reperfusion. In group 4, subjects received a single dose of 50 mg/kg MP intraperitoneally in the 30th minute of ischemia. Kidneys of all subjects were removed after 24 hours. Extracted tissues were investigated regarding histological and biochemical parameters. Results: Malondialdehyde dthe end product of lipid peroxidation as an important indicator of I/R injurydlevels were significantly lower in group 3 than in group 2 (P < 0.05). Malondialdehyde levels were also lower in group 4 than in group 2, but this difference was insignificant (P > 0.05). Superoxide dismutase and glutathione peroxidase enzyme activities were found to be significantly higher in group 3 than in group 2 (P < 0.05). However, there was no difference between group 4 and group 2 in terms of these activities. Histological examination demonstrated that both MP and FM had protective effects against I/R injury, but this effect was more potent for FM than for MP. Conclusions: FM has a protective effect against reperfusion injury in rat kidney after distant organ ischemia.