scholarly journals Catalase activity as signal of antioxydant system affection under influence of limb ischemia-reperfusion

2021 ◽  
pp. 24-30
Author(s):  
Nataliya Volotovska

The use of hemostatic tourniquet is a proved means of primary care. However, systemic disorders, as well as ultrastructural, in the area of compression can significantly worsen the condition of the injured organism. The aim. Estimation of catalase level in rats’ liver on the background of modifications of ischemic-reperfusion syndrome to know the severest pathogenic combination for organism. Materials and methods. 260 white adult male rats were divided into 5 groups: control (KG), EG1 – simulation of isolated ischemia-reperfusion syndrome (IRS) of the limb, EG2 – simulation of isolated volumetric blood loss, EG3 – combination of IRS of the limb with blood loss, EG4 – simulation of isolated mechanical injury of the thigh, EG5 – combination of IRS of the limb and mechanical injury. The variability of catalase level in liver was analyzed. Results. It was found that each of the experimental interventions has led to changes of catalase activity in the liver. The most expressed pathological expressions were observed on the 3rd after interventions, when the studied index in EG3 was lower than in EG1 and EG2 in 6,2 times and by 33,1 %. On the 7th day catalase activity in EG3 was in 9,4 times and by 44,5 % times lower than in EG1 and in EG2 data concordantly. The combination of limb ischemia-reperfusion with blood loss in EG3 led to exhausting of liver antioxydant enzyme catalase in the most critical posttraumatic period (day 3). The same, but less significant effect was registered in the group of combination of mechanical trauma with ischemia-reperfusion in EG5. This proved the role of the tourniquet as a factor that complicated the course of traumatic disease due to ischemic reperfusion. Conclusions. In this experiment, founded risk factors of combination of ischemia-reperfusion with heavy blood loss emphasized the importance and particular attention on such widespread method of bleeding tratment, as the imposition of a tourniquet, as in our experiment it triggered risk factors of ischemia-reperfusion. It was shown katalase activity depression respectively to the periods of increasing of lipid peroxydation. There was peculiarity, that on the base of isolated IRS catalase activity was increased in 2,5 times comparely to control group, whereas the hardest depression of it was found on the background of IRS, combined with blood loss – catalase activity was lower, comparely to KG – in 2,5 times. The importance of understanding the suppression of hepatocytes’ antyoxydants is great, as it might help in prevention the development of liver failure or hepatorenal syndrome on the background of limb ischemia-reperfusion.

Author(s):  
N. V. Volotovska ◽  
A. A. Hudyma

Nowadays stop the bleeding and fight against its consequences determines further success in the survival and rehabilitation of the victim. It is extremely important to find ways to improve the ischemic metabolism as a result of overlaying a tissue turnstile. Enzymes of the glutathione system are actively involved in combating the effects of hypoxia, therefore, the experimental detection of critical periods of depression of this protectional link is the basis for the further search for effective methods of correction and condition stabilization of the affected organism.The aim of the study – to determine the role of glutathione system of the liver and kidneys in the pathogenesis of experimental ischemia-reperfusion (EIR) in the early and remote post-traumatic periods.Materials and Methods. The object of the study – 196 males of white male rats with a body weight 220–240 g, divided into 4 groups, 10 individuals in each. Animals of the control group were withdrawn from the study without surgical intervention, while in the experimental groups, injuries were simulated: a hemostatic tourniquet on the thigh (J) over two hours; isolated blood loss from the femoral vein (40%) – (K); two-hour ischemia, combined with blood loss (J + K) and two-hour ischemia, combined with blood loss and mechanical trauma (J + K + P). The animals were withdrawn from the experiment at 1, 3, 7 and 14 days after the intervention by total bleeding from the heart.Results and Discussion. According to the activation of the lipid peroxidation, which was represented by the growth of the concentration of malonic dialdehyde, diene and trienic conjugates, an active response from the glutathione system was detected: the activation of glutathioneperoxidase activity, an increase of glutathionereductase activity against the decrease restored glutathione concentration. But in the kidney tissue the activity of glutathione system enzymes was somewhat lower, herewith in some periods, conversly, they exceeded liver parameters. These results, in our opinion, indicate that the reason of such their dividing, mainly, it is total debilitation of the glutathione system in the posttraumatical period. It was 1 and 3 days after trauma and partly depended of the injury severity. At the same time, even an isolated overlay of the hemostatic tourniquet led to significant changes of the glutathione system and was represented by response to the activation of lipid peroxidation. This confirms the necessity to continue the series of experiments.Conclusions. The obtained results of the experiments revealed a significant inhibition of the reduced glutathione concentration in the liver, and no so expressed in the kidneys. Especially depression of its activity was on the background of bleeding associated with ischemia, and bleeding associated with ischemia and mechanical trauma. Decrease of glutathioneperoxidase and glutathionereductase activity coincided with increase of lipid peroxidation.


2021 ◽  
Vol 11 (1) ◽  
pp. 351-360
Author(s):  
I. Strelbytska ◽  
A. Hudyma

Introduction. In the structure of modern injuries in wartime and peacetime the share of gunshot wounds increased significantly. The timeliness of applying a tourniquet is one of the main methods of saving lives on the battlefield. The patterns of formation of enteral insufficiency syndrome in conditions of acute blood loss complicated by ischemia-reperfusion of the limb have not been studied enough. There are no data on the features of violations of the absorption function of the small intestine in these conditions and the effectiveness of correction with Carbacetam, which is able to reduce the manifestations of acute hemic hypoxia and ischemic-reperfusion syndrome.The objective of research: To establish the peculiarities of the absorption function of the small intestine in the pathogenesis of acute blood loss, ischemia-reperfusion of the limb and their combination. To evaluate the effectiveness of Carbacetam in the correction of identified abnormalities.Materials and methods. The experimental studies were conducted on 108 white nonlinear male rats weighing 200-220 g, which were housed in standard vivarium conditions. All animals were divided into five groups: control and four experimental. Under thiopental-sodium anesthesia in the first experimental group was simulated ischemia-reperfusion of the limb, in the second group – acute blood loss, and in the third group – these injuries were combined. In the fourth experimental group, animals with acute blood loss and ischemia-reperfusion of the limb were intraperitoneally administered Carbacetam at a dose of 5 mg per kilogram of animal weight. After 1 and 2 hours, as well as after 1, 7 and 14 days studied the absorption function of the intestines by D-xylose test.The results and discussion. Simulation of limb ischemia-reperfusion compared with the control group causes a decrease in the content of D-xylose in the urine after 1 day of the reperfusion period. Also, acute blood loss is accompanied by a significant decrease in this indicator after 1 day. Until the end of the experiment the rate increases, but up to 14 days does not reach the level of control. The combination of acute blood loss and ischemia-reperfusion of the limb causes a decrease in the content of D-xylose in the urine starting from 1 hour of the experiment, which reaches a minimum after 1 day and remains at the same level until 14 days. In these terms the rate was the lowest compared to other studied groups. The use of Carbacetam for corrective purposes in rats with acute blood loss complicated by ischemia-reperfusion of the limb, compared with animals without correction significantly reduces the detected abnormalities after 7 days and more after 14 days of use.Conclusions. Complications of acute blood loss by ischemia-reperfusion of the limb causes a significant decrease in the absorption function of the small intestine after 1 day of the experiment. The intensity of disorders was significantly higher compared to other experimental groups. The use of Сarbacetam for 7-14 days in the reperfusion period in animals with acute blood loss complicated by limb ischemia-reperfusion, compared with animals without correction, causes a significant increase in the absorption function of the small intestine. This indicates the protective effect of the drug under the conditions of simulated pathology.


2020 ◽  
Vol 10 (12) ◽  
pp. 382-393
Author(s):  
Nataliya Volotovska

Among the current medical and social problems, injuries and blood loss occupy a prominent place, causing stress on the antioxidant defenses. Hypoxia, which underlies the pathogenesis of the post-traumatic period of both diseases, leads to a significant imbalance in the work of internal organs. Scientists are increasingly attracted by the need to use a tourniquet or intraoperative ligatures, as reperfusion local and systemic damage develops. Antioxidants are considered a promising means of correction.The aim of the study was to investigate the features of metabolic disorders in the liver in the early post-traumatic period on the background of the use of a tourniquet and the effectiveness of thiocetam correction.Materials and methods. The experiment was perfomed on 130 white male rats (200-250 g), which were divided into 4 groups: control – the CG, the EG-1 – combination of limb ischemia-reperfusion (IR) with blood loss, the EG-2 – combination of limb IR with blood loss and mechanical trauma of the thigh; the EG-3 combination of limb IR, blood loss, mechanical injury and thiocetam administration. The Malonic dialdehide level catalase activity were estimated in the liver.Results. The use of thiocetam, which is able to struggle against of ischemia and lipid peroxidation by reactivating antiradical enzymes: superoxide dismutase, catalase and glutathione peroxidase, had a positive effect on the state of antioxidant and prooxidant units in the organ, located far from the place of primary ischemia-reperfusion. If in the group of untrated animals (the EG-2, where massive blood loss was combined with a thigh fracture and the use of hemostatic tourniquet) in the early period, the MDA level exceeded the CG data in 5,4 times, and on the 7th and 14th days remained high – being higher on 2,1 times and on 2,7 times, then in the EG-3 (group of treated animals) on the 1st day the level of MDA exceeded the CG data in 4,3 times, but on the 7th and 14th days was higher by 90,5 % and 64 % respectively. The supportive effect of thiocetam on the activity of catalase in the liver was also noted. Thus, in EG-2 the level of antioxidant enzyme on the 1st day decreased by 71,7 %, and remained almost at this level throughout the all post-experimental period. As for the group of treated animals, the level of activity on the 1st day after the intervention decreased by 44,7%, and was so for almost the entire period. On the 14th day, it remained reduced compared to the CG by 35,1 %, while in EG-2 this index was lower compared to the CG by 70,5 %.Conclusion. Having the positive effect of the introduction of thiocetam in the ischemic area, we can eventually add new complex, given the world experience, which would affect the development of the inflammatory response and the rheological properties of blood.


2018 ◽  
Vol 16 (1) ◽  
pp. 709-715
Author(s):  
Jana Mašlanková ◽  
Štefan Tóth ◽  
Vladimíra Tomečková ◽  
Tímea Tóth ◽  
Matan Katz ◽  
...  

AbstractIschemic-reperfusion injury of the small intestine is an acute clinical condition with high mortality rate. This study describes the changes in levels of phenylalanine and tryptophan metabolites in intestinal homogenates and urine samples of Wistar male rats after 60 minutes of mesenteric ischemia and different reperfusion periods (1, 24, 30 hours) in comparison with a control group without the ischemia. The ischemic-reperfusion injury was quantified by the histopathological injury index. The levels of serotonin, epinephrine, and norepinephrine were determined in the intestinal homogenate and epinephrine, vanillylmandelic acid, and the 5-hydroxyindoleacetic acid was analyzed in urine using the HPLC method. The statistically significant increased level of serotonin, epinephrine and norepinephrine were detected in the intestinal samples after 24 hours of reperfusion (p<0.01); even the most elevated serotonin level was observed after one hour of reperfusion (p<0.001). A statistically significant decreased level of vanillylmandelic acid was observed after one hour of reperfusion, but it significantly increased after 24 hours (p<0.05) in urine. The elevated level of the 5-hydroxyindoleacetic acid after one hour and 24 hours after reperfusion (p<0.05) were determined in the urine. The most significant elevated epinephrine level was observed after 24 hours of reperfusion (p<0.001) in urine. Results showed a potential role of serotonin as an early biomarker (after one hour of reperfusion) of small intestinal damaged homogenate, while the best predictor of intestinal injury in urine was epinephrine, which was elevated after 24 hours.


2020 ◽  
Vol 10 (12) ◽  
pp. 394-405
Author(s):  
I. Strelbytska ◽  
A. Hudyma

Introduction. In the structure of injuries from gunshot wounds dominate the limb injuries that are often complicated by massive bleeding from the main vessels. The only means of rescue on the battlefield is a timely application of a tourniquet. This ensures complete exsanguination of the limb. The duration of exsanguination should not exceed 2 hours. It is proved that in conditions of acute blood loss complicated by ischemia-reperfusion of the limb, there are prerequisites for the development of dysfunction of internal organs, which in turn exacerbates dysmetabolic and functional disorders, stimulates endotoxicosis and may be complicated by multiple organ failure. However, the patterns of formation of the syndrome of endogenous intoxication in the conditions of ischemia-reperfusion of the limb, acute blood loss and their combinations have not been studied. There are no data on the effect of Carbacetam on these processes. It is known that Carbacetam has proven itself to reduce the manifestations of dysfunction of internal organs in the conditions of ischemic-reperfusion syndrome of the limb.The objective of research: To establish the dynamics of endogenous intoxication in the conditions of ischemia-reperfusion of the limb, acute blood loss and their combination. To evaluate the effectiveness of Carbacetam in the correction of identified abnormalities.Materials and methods. The experimental studies were conducted on 108 white nonlinear male rats weighing 200-220 g, which were housed in standard vivarium conditions. All animals were divided into five groups: control and four experimental. Under thiopental-sodium anesthesia in the first experimental group was simulated ischemia-reperfusion of the limb, in the second – acute blood loss, and in the third – these injuries were combined. In the fourth experimental group, animals with acute blood loss and ischemia-reperfusion of the limb were intraperitoneally administered Carbacetam at a dose of 5 mg per kilogram of animal weight. After 1 and 2 hours, as well as after 1, 7 and 14 days in the blood serum was determined the content of middle-mass molecules (MMM254, MMM280).The results and discussion. It was found that ischemia-reperfusion of the limb in comparison with the control group is accompanied by a significant increase of the MMM254 fraction in the blood serum content. From the first hour of the experiment with a maximum after 1 day and normalization of the index up to 14 days. The content in the blood serum of the MMM280 fraction became significantly higher, from the control only after 1 day with subsequent normalization in the following terms of the experiment. After simulation of acute blood loss, both studied fractions of MMM increased from 1 hour of the experiment, reached a maximum after 1 day and did not return to the control level after 14 days. For the first time it was found that two-hour ischemia-reperfusion of the limb significantly aggravates the course of acute blood loss, which revealed a significantly higher content in the serum of fractions MMM254 and MMM280 compared to other experimental groups in almost all periods of the experiment. Due to the use of Carbacetam, the content of both studied fractions of MMM in the serum compared with animals without correction was significantly reduced after 7 and 14 days of the experiment. Although the studied parameters did not return to the level of the Carbacetam control group, it can be considered a pathogenetically justified means of reducing the level of endotoxicosis in the conditions of ischemia-reperfusion of the limb and acute blood loss.Conclusions. Simulation of limb ischemia-reperfusion is accompanied by accumulation of MMM254-280 fractions with a maximum after 1 day of the experiment and normalization up to 14 days. Acute blood loss causes an increase in the serum content of fractions MMM254-280 from 1 hour of the experiment, which up to 14 days do not reach the level of control. The detected disorders are significantly exacerbated after a combination of acute blood loss and ischemia-reperfusion of the limb. The use of Carbacetam in comparison with animals without correction is accompanied by a significant decrease in the content of MMM254-280 fractions in the serum after 7 and 14 days of the experiment.


Author(s):  
N. V. Volotovska ◽  
T. V. Kashchak

Background. Blood loss during civil and military limb trauma is the most common cause of preventable death. Complications due to the use of a hemostatic tourniquet are widely investigated nowadays. Therefore, the standards of the past have to be improved. Objective. The aim of the research is to study the reaction of the enzyme chain of the liver antioxidant system in the presence of modifications of ischemia-reperfusion injury (IRI). Methods. 210 white male-rats, aged 5-5.5 months, were used in the research. The dynamics of antioxidant enzymes activity catalase (Cat) and superoxide dismutase (SOD) in liver tissue in cases of modifications of ischemia-reperfusion injury (IRI) were studied. The period of investigation was in 24 hours, 3, 7, 14 days after the injury. Results. In cases of simulated IRI the catalase level mainly decreased at each period of the experiment. The peak of SOD activity was evidenced on the 1st, 3rd or 7th days after the experimental IRI according to the degree of trauma severity. Thus, IRI combined with severe blood loss and mechanical trauma caused the severest affection of the antioxidant system. Even a single application of hemostatic tourniquet caused similar wavelike reactions at different times. Conclusions. The development of IRI is accompanied by a significant depression of the liver antioxidant system. The most significant changes were evidenced in cases of IRI combined with blood loss and mechanical trauma, but even a single application of a tourniquet caused active response of the antioxidant enzymes.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jiefeng Xu ◽  
Sen Ye ◽  
Zilong Li ◽  
Moli Wang ◽  
Zhengquan Wang ◽  
...  

Introduction: Systemic ischemia-reperfusion injury produced by CA and resuscitation can result in severe post-cardiac arrest syndrome; which includes systemic inflammatory response and multiple organ dysfunction syndrome such as acute pulmonary edema. We previously demonstrated that remote ischemic post-conditioning (RIpostC) improved post-resuscitation myocardial and cerebral function in a rat model of CA. In this study, we investigated the effects of RIpostC on inflammatory response and pulmonary edema after CPR in a porcine model. Hypothesis: RIpostC would alleviate post-resuscitation inflammatory response and pulmonary edema in a porcine model of CA. Methods: Fourteen male domestic pigs weighing 37 ± 2 kg were utilized. Ventricular fibrillation was electrically induced and untreated for 10 mins. The animals were then randomized to receive RIpostC or control. Coincident with the start of CPR, RIpostC was induced by four cycles of 5 mins of limb ischemia and then 5 mins of reperfusion. Defibrillation was attempted after 5 mins of CPR. The resuscitated animals were monitored for 4 hrs and observed for an additional 68 hrs. Results: Six of the seven animals in each group were successfully resuscitated. After resuscitation, significantly lower levels of tumor necrosis factor-α and interleukin-6 were measured in the animals that received RIpostC when compared with the control group. Post-resuscitation extra-vascular lung water index was lower in the RIpostC group than in the control group; in which the differences were significant at 2,3 and 4 hrs (Table). Conclusion: In a porcine model of CA, RIpostC significantly alleviates post-resuscitation inflammatory response and pulmonary edema.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Zhongzhong Liu ◽  
Xingjian Zhang ◽  
Qi Xiao ◽  
Shaojun Ye ◽  
Chin-Hui Lai ◽  
...  

Objective. Severe hepatic ischemia reperfusion injury (IRI) can result in poor short- and long-term graft outcome after transplantation. The way to improve the viability of livers from donors after circulatory death (DCD) is currently limited. The aim of the present study was to explore the protective effect of simvastatin on DCD livers and investigate the underlying mechanism. Methods. 24 male rats randomly received simvastatin or its vehicle. 30 min later, rat livers were exposed to warm ischemia in situ for 30 min. Livers were removed and cold-stored in UW solution for 24 h, subsequently reperfused for 60 min with an isolated perfused rat liver system. Liver injury was evaluated during and after warm reperfusion. Results. Pretreatment of DCD donors with simvastatin significantly decreased IRI liver enzyme release, increased bile output and ATP, and ameliorated hepatic pathological changes. Simvastatin maintained the expression of KLF2 and its protective target genes (eNOS, TM, and HO-1), reduced oxidative stress, inhibited innate immune responses and inflammation, and increased the expression of Bcl-2/Bax to suppress hepatocyte apoptosis compared to DCD control group. Conclusion. Pretreatment of DCD donors with simvastatin improves DCD livers’ functional recovery probably through a KLF2-dependent mechanism. These data suggest that simvastatin may provide a potential benefit for clinical DCD liver transplantation.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Orhan Cimen ◽  
Hüseyin Eken ◽  
Ferda Keskin Cimen ◽  
Arif Burak Cekic ◽  
Nezahat Kurt ◽  
...  

Abstract Background Liver ischemia reperfusion (I/R) damage which is frequently seen in clinical hepatobiliary surgeries has no effective treatment for it. Liv-52, known to have hepatoprotective effects, is a natural antioxidant drug licensed by the Ministry of Health of India. The aim of our study is to investigate the effect of Liv-52 on liver damage induced by I/R in rats. Methods Albino Wistar male rats were divided into three groups; liver I/R (IR), 20 mg/kg Liv-52 + liver ischemia reperfusion (LIR) and sham operation applied to control group (HG). Liv-52 was administered to the LIR group (n = 6) 1 h prior to I/R application and distilled water was given orally to IR (n = 6) and HG (n = 6) groups as a solvent. Ischemia was determined as 1 h, and reperfusion was identified as 6 h in animals. Results Increased levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, malondialdehyde, myeloperoxidase, and decreased levels of superoxide dismutase, and glutathione related enzymes caused by I/R application have been converged to healthy group level with Liv-52 treatment and the damage in liver tissue has been improved histopathologically. Conclusions Liv-52 may be beneficial for preventing liver I/R damage in pre-surgery application.


2020 ◽  
Author(s):  
Jianzhao Chen ◽  
Yushuang Chai ◽  
Yuanfeng He ◽  
Jisheng Huang ◽  
Ting Wan ◽  
...  

Abstract Background: Investigate the different treatment course of ANP from pharmacology and toxicology to provide scientific basis for clinic use. Method: In pharmacology study, cerebral ischemia-reperfusion model was made; rats were divided into six groups, Sham, model, aspirin 25 mg/kg, ANP 270 mg/kg (1 day, 4 days and 7 days) groups. Rats were fed for 30 days. Neurological function, cerebral infraction volume, brain histopathology, cytokines were detected; in toxicology study, rats were divided into four groups, normal control, ANP (550, 1640, 4910 mg/kg) group. ANP was daily administered by gavage for 30 days. Detection indicators included appearance, behavior, excrement character, food-intake, body weight, hematological parameters, etc. In addition, biomarkers such as TBA, GSTα, Cystatin C, clusterin, GSH, S-100B and MBP were also detected. Result: In pharmacology study, compared with model group, the neurological function scores of ANP 270mg/kg (1 day, 4 days and 7 days) were decreased (P<0.11 or P<0.05); the volume of ANP 270mg/kg (1 day and 7 days) were decreased (P<0.05); the R value of ANP 270mg/kg (1 day, 4 days and 7 days) groups were decreased (P<0.11 or P<0.05); the serum content of IL-1β, TNFα and NO of ANP 270 mg/kg(1 day, 4 days and 7 days) groups were decreased (P< 0.05); the brain content of IL-1β and NO of ANP 270 mg/kg(1 day, 4 days and 7 days) groups were decreased (P<0.05). In toxicology study, no mortality, ophthalmic abnormalities were identified. Compared with normal control group, body weights were significantly lower in ANP 4910 mg/kg group; TBA was significantly increased in ANP 4910mg/kg group; liver organ coefficient of female rats of ANP 4910 mg/kg group was increased (P < 0.05); kidney organ coefficient of male rats of ANP 1640mg/kg, 4910 mg/kg groups were increased (P < 0.05), these all recovered after drug withdraw for 8 weeks. Conclusion: The effect of ANP 270 mg/kg (7 days) was much better than ANP (1 day and 4 days). ANP 550mg/kg is non toxicity dose. So, ANP is taken one pill peer day for 7 days is safety and effective, it can be used as the scientific basis for clinic use.


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