Dexmedetomidine protects against myocardial ischaemia/reperfusion-induced renal damage in rats (original) (raw)
Related papers
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...
Archives of Physiology and Biochemistry, 2020
Objectives: This study investigated the effect of dexmedetomidine on the oxidant-antioxidant (thiol/ disulphide) balance. Methods: A total of 24 rats were divided into four groups. The renal arteries in groups IR (ischaemia/ reperfusion) and IR þ D (ischaemia/reperfusion þ dexmedetomidine) were clamped for 45 min and reperfused for 180 min. Groups D (Dexmedetomidine) and IR þ D were administered 100 lg/kg dexmedetomidine. Oxidant-antioxidant (thiol/disulphide) levels were measured. Kidney tissue was examined histopathologically. Results: No statistically difference was found between the groups in terms of thiol-disulphide averages, while IMA, TOS and thiol-disulphide results showed a minimal decrease in Group IR þ D compared to Group IR (p > 0.05). Tubular lesions and necrosis were found in 26-50% of tubules in Group IR. Tubular damage and necrosis in Group IR þ D declined to 5-25%. Conclusions: No statistically difference was found in the study where OSI index, thiol/disulphide balance and IMA were measured together as biochemical values.
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.
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.
Zenodo (CERN European Organization for Nuclear Research), 2022
Background: In this study it is aimed to compare the effects of Dexmedetomidine (Dex) and Thymoquinone (TQ) on kidney at hind limb ischemia/reperfusion injury generated rats Materials and Methods: 50 Wistar albino rats were included to the study. Rats were divided into 5 groups (n=10) as Sham, Control, TQ, Dex, and Dex-TQ. After anesthesia was given to the rats, ischemia was performed to left hind limb for 4 hours and then 2 hours reperfusion applied. TQ and Dex were administered intraperitoneally after the end of 4 hours ischemia and 5 minutes before start of reperfusion. At the end of study all rats were sacrificed. Blood and kidney samples were taken to evaluate Total Antioxidant Status (TAS), Total Oxidant Status (TOS) Oxidative Stress Index (OSI) values and histopathological examination. Results: TAS value was measured that the lowest value in Control Group (0.07±0.01). TAS values of TQ, Dex, Dex-TQ groups were significantly higher than those of Control Group (p<0.05). There was no significant difference between TQ, Dex, Dex-TQ groups regarding to TAS values (p>0.05). TOS values were measured and they were the highest in the Control Group and the lowest in the Sham Group (p<0.05 for all). TOS values of TQ, Dex, Dex-TQ groups significantly lower than those of the Control Group (p<0.05) and significantly higher than those of the Sham Group (p<0.05). There was no significant difference between TQ, Dex, Dex-TQ groups regarding to TOS values (p>0.05). OSI values of TQ, Dex, Dex-TQ groups significantly lower than those of the Control Group (p<0.05) and higher than those of the Sham Group (p<0.05 for all). There was no significant difference between TQ, Dex, Dex-TQ groups regarding to OSI values (p>0.05 for all). The histopathological damage score was the lowest in the Sham group and the highest in the Control group. While there was no significant difference between Sham, TQ, Dex, Dex-TQ groups (p>0.05); It was found to be significantly lower when compared to the control group (p<0.05). Conclusion: Histopathological changes were observed at kidney in hind limb ischemia/reperfusion due to oxidative stress. TQ and Dex had protective effects on renal tissues at ischemia/reperfusion injury.
Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury
Kidney ischemia-reperfusion (I/R) injury is a common cause of acute kidney injury. We tested whether dexmedetomidine (Dex), an alpha2 adrenoceptor (a2-AR) agonist, protects against kidney I/R injury. Sprague-Dawley rats were divided into four groups: (1) Sham-operated group; (2) I/R group (40 min ischemia followed by 24 h reperfusion); (3) I/R group + Dex (1 lg/kg i.v. 60 min before the surgery), (4) I/R group + Dex (10 lg/kg). The effects of Dex postconditiong (Dex 1 or 10 lg/kg i.v. after reperfusion) as well as the effects of peripheral a2-AR agonism with fadolmidine were also examined. Hemodynamic effects were monitored, renal function measured, and acute tubular damage along with monocyte/macrophage infiltration scored. Kidney protein kinase B, toll like receptor 4, light chain 3B, p38 mitogen-activated protein kinase (p38 MAPK), sirtuin 1, adenosine monophosphate kinase (AMPK), and endothelial nitric oxide synthase (eNOS) expressions were measured, and kidney transciptome profiles analyzed. Dex preconditioning, but not postconditioning, attenuated I/R injury-induced renal dysfunction, acute tubular necrosis and inflammatory response. Neither pre-nor postconditioning with fadolmidine protected kidneys. Dex decreased blood pressure more than fadolmidine, ameliorated I/R-induced impairment of autophagy and increased renal p38 and eNOS expressions. Dex downregulated 245 and upregulated 61 genes representing 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, in particular, integrin pathway and CD44. Ingenuity analysis revealed inhibition of Rac and nuclear factor (erythroid-derived 2)-like 2 pathways, whereas aryl hydrocarbon receptor (AHR) pathway was activated. Dex preconditioning ameliorates kidney I/R injury and inflammatory response, at least in part, through p38-CD44-pathway and possibly also through ischemic preconditioning.
Turkish Journal of Anesthesia and Reanimation, 2018
The aim of this study was to investigate the effects of dexmedetomidine before and after ischaemia in diabetic rat kidney ischaemia reperfusion (IR) injury in the experimental diabetic rat model. Methods: Data belonging to 35 rats weighing between 250 and 300 g were analysed. Diabetes mellitus (DM) was induced using streptozotocin. Groups had bilateral renal vasculature clamped for 45 min ischaemia before clamps were removed, and 4 hours reperfusion was applied. Rats were divided into five groups: Group I or nondiabetic sham group (n=7), Group II or diabetic sham group (n=7), Group III or diabetic IR group (n=7), Group IV or diabetic IR+prophylactic Dex P (before ischaemia) (n=7) and Group V or diabetic IR+therapeutic Dex T (following reperfusion) (n=7). Dexmedetomidine was administered at a dose of 100 μg kg-1 intraperitoneally. Histomorphological and biochemical methods were used to assess the blood and tissue samples. Results: The proximal tubule injury score in the control sham group was significantly lower than in other groups. The proximal tubule and total cell damage scores of the diabetic IR group were significantly higher than the diabetic IR+Dex T group, and no significant difference was detected in the diabetic IR+Dex P group. The biochemical parameters of the IR group were significantly increased compared to Groups I and II; however, there was no significant reduction in these parameters in the groups administered dexmedetomidine. Conclusion: Although administration of dexmedetomidine after ischaemia in the diabetic rat renal IR model was found to be more effective on the histopathological injury scores compared to preischaemic administration, this study has not shown that dexmedetomidine provides effective and complete protection in DM.
Renal failure, 2015
Background: Ischemic acute kidney injury is a common occurrence in the perioperative period and in critical patients admitted to intensive care units. The reestablishment of blood supply may worsen injury through the ischemia-reperfusion (I/R) mechanism. We investigated the effect of dexmedetomidine on the kidneys of rats subjected to an experimental I/R model. Methods: 34 rats anesthetized with isoflurane was undergone right nephrectomy and randomly assigned to four groups: Control C (saline solution); Dexmedetomidine D (dexmedetomidine); Sham S (saline solution); Sham with Dexmedetomidine SD (dexmedetomidine). The serum levels of neutrophil gelatinase-associated lipocalin (NGAL) were measured at time-points T1 (following stabilization), T2 (ischemia), T3 (reperfusion), T4 (12 h after of I/R). The kidneys were subjected to histological examination. Results: The NGAL levels were significantly higher at T4 compared with T1. Upon histological examination, the left kidneys in groups C ...