Lower Extremity Ischemia Reperfusion Injury Research Articles

The Effect of Cerium Oxide (CeO2) on Ischemia-Reperfusion Injury in Skeletal Muscle in Mice with Streptozocin-Induced Diabetes.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, in temporary clamping of the aorta in aortic surgery, or following acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress such as DM. Cerium oxide (CeO2) nanoparticles mimic antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n = 6), diabetes group (group D, n = 8), diabetes-CeO2 (group DCO, n = 8), diabetes-ischemia/reperfusion (group DIR, n = 8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n = 8). The DCO and DIRCO groups were given doses of CeO2 of 0.5 mg/kg intraperitoneally 30 min before the IR procedure. A 120 min ischemia-120 min reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p = 0.047 and p = 0.022, respectively). In group DIRCO, total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p < 0.001). The oxidative stress index (OSI) was found to be significantly lower in group DIR compared with group DCO (p < 0.001). Paraoxanase (PON) enzyme activity was found to be significantly increased in group DIR compared with group DCO (p < 0.001). The disorganization and degeneration score for muscle cells, inflammatory cell infiltration score, and total injury score in group DIRCO were found to be significantly lower than in group DIR (p = 0.002, p = 0.034, and p = 0.001, respectively). Conclusions: Our results confirm that CeO2, with its antioxidative properties, reduces skeletal muscle damage in lower extremity IRI in diabetic mice.

The Effect of Sevoflurane and Fullerenol C 60 on the Liver and Kidney in Lower Extremity Ischemia-Reperfusion Injury in Mice with Streptozocin-Induced Diabetes.

This study aimed to demonstrate whether fullerenol C60, sevoflurane anesthesia, or a combination of both had protective effects on the liver and kidneys in lower extremity ischemia-reperfusion injury (IRI) in mice with streptozocin-induced diabetes. A total of 46 Swiss albino mice were divided into six groups as follows: control group (group C, n=7), diabetes group (group D, n=7), diabetes-ischemia/reperfusion (group DIR, n=8), diabetes-ischemia/reperfusion-fullerenol C60 (group DIR-FC60, n=8), diabetes-ischemia/reperfusion-sevoflurane (group DIR-S, n=8), and the diabetes-ischemia/reperfusion-fullerenol C60-sevoflurane (group DIR-S-FC60, n=8). Fullerenol C60 (100mg/kg) was administered intraperitoneally 30 min before the ischemia-reperfusion procedure to the fullerenol groups (DIR-FC60 and DIR-S-FC60). In the DIR groups, 2 hours (h) ischemia-2h reperfusion periods were performed. In the sevoflurane groups, sevoflurane was applied during the ischemia-reperfusion period with 100% O2. Liver and kidney tissues were removed at the end of the reperfusion procedure for biochemical and histopathological examinations. In liver tissue, hydropic degeneration, sinusoidal dilatation, pycnotic nuclei, prenecrotic cells, and mononuclear cell infiltration in parenchyma were significantly more frequent in group DIR than in groups D and group C. In terms of the histopathologic criteria examined, more positive results were seen in group DIR-FC60, and when group DIR-FC60 was compared with group DIR, the difference was significant. The best results in AST, ALT, glucose, TBARS levels, and SOD enzyme activities in liver tissue were in group DIR-FC60 compared with group DIR, followed by groups DIR-S-FC60 and DIR-S, respectively. Regarding TBARS levels and SOD enzyme activities in kidney tissue, the best results were in groups DIR-FC60, DIR-S-FC60, and DIR-S, respectively. According to our findings, it is clear that fullerenol C60 administered intraperitoneally 30 min before ischemia, alone or together with sevoflurane, reduces oxidative stress in distant organ damage caused by lower extremity IRI, and reduces liver and kidney tissue damage in histopathologic examinations.

The effects of different doses of amantadine on lung tissue in lower extremity ischemia reperfusion injury in rats

Aim: Ischemia/reperfusion (I/R) injury is a common complication after abdominal aortic surgery. N-Methyl D-Aspartate (NMDA) antagonists protect many organs against to I/R injury. Therefore, in this study, we aimed to investigate the effects of 135 mg/kg and 90 mg/kg of amantadine, on lung tissue after lower extremity I/R injury in rats.&#x0D; Material and Methods: 36 wistar rats were randomly divided into 6 groups each containing six rats as follows; Sham group (Group S), Amantadine 90 group (Group A-90), Amantadine 135 group (Group A-135), Ischemia/Reperfusion group (Group I/R), Ischemia/Reperfusion + Amantadine 90 group (Group I/R-A 90), Ischemia/Reperfusion + Amantadine 135 group (Group I/R-A 135). At the end of procedure, all rats were sacrificed, and their lung tissues were obtained. Lung tissues were examined biochemical and histopathologically.&#x0D; Results: The lung tissue catalase, superoxide dismutase activities and malondialdehide levels were similar between the groups. Lung tissue neutrophil/lymphocyte infiltration score levels were higher in Group I/R than Group S, Group A-90 and Group A-135. Alveolar wall thickening score levels were higher in Group I/R than Group S, Group A-90, Group A-135 and Group I/R-A 135. &#x0D; Conclusion: Although we could not find a statistically significant difference between lung tissue biochemical values, we observed that lung tissue was histopathologically affected by I/R damage and the damage was less with amantadine use. In the reduction of I/R damage, 135 mg/kg administration of amantadine was more beneficial than 90 mg/kg.

The effect of cerium oxide on lung injury following lower extremity ischemia-reperfusion injury in rats under desflurane anesthesia.

Objectives:To examine the effects of desflurane and cerium oxide (CO) on lung tissue following ischemia-reperfusion injury (IRI).Methods:Experiments were conducted in Gazi University Animal Laboratory, Ankara, Turkey. Thirty rats were divided into 5 groups: control (C), IRI, IRI-CO, IRI-desflurane (IRID), IRI-CO-desflurane (IRICOD). Cerium oxide was given intraperitoneally. Lower extremity IRI was induced. Desflurane was applied during IRI. Lung histopathological examinations and serum biochemical analyses were performed.Results:Serum nitric oxide (NO) and malondialdehyde (MDA) levels were higher in group IRI (p=0.006) than in group C (p=0.001). Serum MDA and NO levels were significantly lower in groups IRICO and IRICOD than in group IRI. Significantly greater alveolar wall thickening and neutrophil infiltration were recorded in group IRI than in group C. Co-administration of desflurane and CO significantly decreased alveolar wall thickening and neutrophil infiltration compared to group IRI. Total lung injury scores were significantly lower in groups IRID, IRICO, and IRICOD than in group IRI.Conclusion:Intraperitoneal CO with desflurane, reduced oxidative stress and corrected the damage in lung. Cerium oxide given before and desflurane given during IRI have been shown to have protective effects on lung damage in rats.

The Effect of Cerium Oxide on Lung Tissue in Lower Extremity Ischemia Reperfusion Injury in Sevoflurane Administered Rats.

IntroductionWe aimed to investigate the effects of cerium oxide, applied before the sevoflurane anesthesia, on lung tissue in rats with lower extremity ischemia-reperfusion (IR).Materials and MethodsA total of 30 rats were randomly divided into five groups as; control (C), IR, cerium oxide-IR (CO-IR), IR-sevoflurane (IRS), and cerium oxide-IR-sevoflurane (CO-IRS). In the CO-IR group, 30 minutes after the injection of cerium oxide (0.5 mg/kg, intraperitoneal (i.p)), an atraumatic microvascular clamp was placed on the infrarenal abdominal aorta for 120 minutes. Then, the clamp was removed and reperfused for 120 minutes. Sevoflurane was applied in 100% oxygen at a rate of 2.3% at 4 L/min during IR. The blood samples were taken for biochemical analysis and the lung tissue samples were taken for histological analysis.ResultsNeutrophil infiltration/aggregation was significantly higher in the IR group than in the C and CO-IRS groups. The alveolar wall thickness and total lung injury scores were significantly higher in the IR group than in the C, IRS, CO-IR and CO-IRS groups.DiscussionWe determined that the administration of 0.5 mg/kg dose of cerium oxide with sevoflurane reduces the oxidative stress and corrects IR-related damage in lung tissue. Our results show that the administration of cerium oxide before IR and the administration of sevoflurane during IR have a protective effect in rats.

Rat Alt Ekstremite İskemi Reperfüzyon Hasarının Tenoksikam ile Önlenmesi

Rat Alt Ekstremite İskemi Reperfüzyon Hasarının Tenoksikam ile Önlenmesi

Effect of Dexmedetomidine on Lung Tissue Lower Extremity Ischemia Reperfusion Injury in Streptozotocin Induced Diabetic Rats

Effect of Dexmedetomidine on Lung Tissue Lower Extremity Ischemia Reperfusion Injury in Streptozotocin Induced Diabetic Rats

The investigation of the preventive effects of Coenzyme Q10 and Berberine for tourniquet induced ischemia-reperfusion injury on skeletal muscle in rat hindlimb

In this study, the role of CoQ10 and berberine in the treatment of ischemia-reperfusion injury is researched by analyzing the biochemical effects of CoQ10 and berberine administered after experimental ischemia-reperfusion injury in rats. 32 Sprague-Dawley 200-250 g male rats were randomly divided into four equal groups as weighting, including: control, ischemia-reperfusion (I/R) and experimental groups treated with CoQ10 (10 mg/kg dose, 3 times with 8 h intervals) and berberine (200 mg/kg dose, 3 times with 8 h intervals) that were administered by intragastric way to the I/R+ CoQ10 and I/R+ berberine group before two hours ischemia two hours reperfusion with tourniquet. In the sham group, only gastrocnemius muscle were removed and given no CoQ10 and Berberine. By the completion of reperfusion; all rats were anesthetized with ketamine and xylazine, sacrificed after taking samples to measure levels of blood lactate dehydrogenase (LDH), creatine kinase (CK); MDA, MPO, GSH, SOD, GPx and CAT in blood and muscle tissues. Compared to control group, ischemic-reperfusion injury significantly increased plasma LDH, CK; MDA and MPO levels, decreased GSH, SOD, GPx and CAT activities of blood and muscle tissues. Treatments groups showed significantly decreased MDA and MPO levels, increased GSH levels, SOD, GPx and CAT activities compared to the IR group. Our results suggest that CoQ10 and Berberine may protect or treat against oxidative damage on ischemia-reperfusion injury and that can be benefical treating association with lower extremity ischemia-reperfusion injury.

Effect of microRNA-26a on vascular endothelial cell injury caused by lower extremity ischemia-reperfusion injury through the AMPK pathway by targeting PFKFB3.

Vascular endothelial cell (VEC) dysfunction plays an important role in the ischemia-reperfusion injury (IRI)-related diseases, and microRNAs (miRNAs) are key factors during this process. We conducted this study to investigate whether miRNA-26a (miR-26a) has effect on the IRI-induced VEC injury via the AMPK pathway by targeting 6-phosphofructo-2-kinase-fructose-2,6-biphosphatase 3 (PFKFB3). IRI rat models were successfully constructed by an abdominal incision. Additionally, the cultured VECs were further treated with miR-26a mimic or inhibitor, and si-PFKFB3. Both the reverse-transcription quantitative polymerase chain reaction and the western blot assay method were carried out to examine the expressions of PFKFB3, endothelial nitric oxide synthase (eNOS), and 5'-adenosine monophosphate-activated protein kinase (AMPK) α1, as well as the extent of the AMPK α1 phosphorylation levels in vascular tissues. Circulating endothelial cell (CEC), von Willebrand factor (VWF), thrombomodulin (TM), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and endothelin (ET) were all measured. In the rat model of an IRI, a poorly expressed miR-26a and contrarily highly expressed PFKFB3 were identified in vascular tissues. In response to an overexpression of miR-26a or to the PFKFB3 gene silencing, decreased CEC number, TM, VWF, MDA, and ET contents, increased AMPK α1, and eNOS levels, as well as the extent of AMPK α1 phosphorylation coordinate with both increased SOD and NO contents based on the restoration of the AMPK pathway. Overexpression of the miR-26a or si-PFKFB3 provides an elevation in cell proliferation. Our study suggests that the miR-26a RNA alleviates lower extremity IRI-induced VEC injury in rats through the activation of the AMPK pathway by inhibiting PFKFB3.

Effects of dexmedetomidine on renal tissue after lower limb ischemia reperfusion injury in streptozotocin induced diabetic rats

ABSTRACTAim: The aim of this study was to investigate whether dexmedetomidine – administered before ischemia – has 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 dexmedetomidine-treated 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 intraperitoneally – administered 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.

An investigation on the impact of carnosine on the myocardium in lower extremity ischemia-reperfusion injury in rats

The purpose of this study was to investigate the effect of carnosine (CAR) on ischemia-reperfusion (I-R) injury to the myocardium occurring after occlusion reperfusion of the infrarenal abdominal aorta (IAA) in rats. In this study, 30 Sprague-Dawley rats were randomly divided into three equal groups which are control, I-R, and I-R+CAR groups. Laparotomy and IAA dissection were performed in all groups; occlusion was not performed in the control group. In the control group, the process was completed in 90min as in the other two groups. In the I-R and I-R+CAR groups, the IAA was occluded by microvascular clamps; the first 30min represented the ischemia period, followed by declamping and a 60min reperfusion period. After the I-R period, rats were sacrificed. Heart specimens and blood samples were taken for histopathological and biochemical evaluation. Statistically significant alterations were observed in the control group in comparison with the other groups in the histopathological analyses. Although there was no significant difference between the I-R and I-R+CAR groups regarding the histopathological findings, the I-R+CAR group displayed more favorable histopathological findings compared with the I-R group. There were also significant alterations between the I-R and I-R+CAR groups regarding aspartate aminotransferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH) enzyme levels. The I-R+CAR group had significantly lower enzyme levels compared with the I-R group. In conclusion, carnosine seems to effectively prevent myocardial I-R injury in rats, as demonstrated by histopathological and biochemical evaluation.

An investigation on the impact of carnosine on the myocardium in lower extremity ischemia–reperfusion injury in rats

An investigation on the impact of carnosine on the myocardium in lower extremity ischemia–reperfusion injury in rats

Comparison of effects of sevoflurane versus propofol on tourniquet-induced lower extremity ischemia-reperfusion injury in patients undergoing orthopedic operation

Objective To compare the effects of sevoflurane versus propofol on a tourniquet-induced lower extremity ischemia-reperfusion (I/R) injury in patients undergoing orthopedic operation.Methods Fifty-four ASA Ⅰ or Ⅱ patients,aged 18-64 yr,weighing 44-85 kg,scheduled for elective orthopedic operation,were randomly assigned into 3 groups (n =18 each)∶ control group (group C),propofol group (group P) and sevoflurane group (group S).After lumbar plexus-sciatic nerve block,the laryngeal mask airway insertion was facilitated with propofol 2-4 mg/kg and anesthesia was maintained with infusion of propofol at 2-4 mg· kg-1 · h-1 during operation in group P.In group S,8 ％ sevoflurane was inhaled,the laryngeal mask airway was inserted and anesthesia was maintained with inhalation of 2％ sevoflurane during operation.A tourniquet was applied and inflated (300 mm Hg)during 15-20 min after administration of propofol or sevoflurane in groups P and S,and a tourniquet was also applied at the same time point in group C.The tourniquet was released at the end of operation.Postoperative analgesia was performed with oral meloxicam or intramuscular pethidine and VAS score was maintained ＜ 3.Blood samples were taken after admission to the operating room (T1) and 30 min after tourniquet release (T2) to determine the plasma concentrations of MDA and TNF-α.The changing rate of MDA and TNF-α concentrations was calculated.The tourniquet-related adverse events and amount of analgesics consumed within 24 h after operation were recorded.Results No tourniquet-related adverse events occurred in all the patients.Compared with group C,the plasma concentrations of MDA and TNF-α and changing rate were significantly decreased at T2 in groups P and S (P ＜ 0.05).There were no significant differences in the plasma concentrations of MDA and TNF-α and changing rate between group S and group P (P ＞ 0.05).Compared with the baseline value at T1,no significant change was found in the plasma concentrations of MDA and TNF-α at T2 in groups P and S (P ＞ 0.05),and the plasma concentrations of MDA and TNF-α were significantly increased at T2 in group C (P ＜ 0.05).There was no significant difference in the amount of analgesics consumed within 24 h after operation between the three groups (P ＞ 0.05).Conclusion Both sevoflurane and propofol can reduce a tourniquet-induced lower extremity I/R injury in patients undergoing orthopedic operation and the efficacy is comparable. Key words: Anesthetics, inhalation ; Propofol ; Tourniquets ; Reperfusion injury ; Lower extremity

The Challenges of Lower Extremity Ischemia-Reperfusion Injury

The Challenges of Lower Extremity Ischemia-Reperfusion Injury