Local effect of melatonin in an original dermal film limiting lipid peroxidation and accelerating healing in experimental thermal trauma

2021 ◽  
pp. 94-101
Author(s):  
М.В. Осиков ◽  
Е.В. Симонян ◽  
А.А. Агеева ◽  
А.И. Синицкий ◽  
Ю.И. Агеев
Keyword(s):  
Lipid Peroxidation ◽  
Local Therapy ◽  
Pleiotropic Effect ◽  
Local Effect ◽  
Lipid Extract ◽  
Male Rats ◽  
Burn Wound ◽  
Thermal Trauma ◽  
Pleiotropic Regulators ◽  
Injured Skin

Разработка и патогенетическое обоснование новых подходов к локальной терапии термической травмы (ТТ) является актуальной и востребованной проблемой. В частности, представляет интерес разработка дермальных пленок (ДП), содержащих эндогенные регуляторы гомеостаза мультитропного действия. Цель исследования - оценка эффекта мелатонина (МТ) в составе оригинальной ДП на процессы репарации и содержание продуктов перекисного окисления липидов (ПОЛ) в коже очага повреждения при локальной термической травме. Методика. Эксперимент выполнен на 126 крысах-самцах Wistar. ТТ ІІІА степени площадью 3,5% моделировали погружением участка межлопаточной области кожи в очищенную воду с температурой 98-99 ºС на 12 с. МТ в составе ДП (0,005 г/г) на основе натрия карбоксиметилцеллюлозы наносили ежедневно после ТТ в течение 5 сут. На 5-е и 10-е сут после ТТ оценивали макроскопическую картину, площадь и глубину ожоговой раны, скорость ее эпителизации. Содержание продуктов ПОЛ в гомогенате кожи ожоговой раны определяли экстрационно-спектрофотометрическим методом в гептановой и изопропанольной фазах липидного экстракта. Результаты. Установлено, что накопление вторичных и конечных продуктов ПОЛ в гептановой и изопропанольной фазах липидного экстракта на 5-е и 10-е сут ассоциировано с площадью ожога. Применение оригинальной ДП с мелатонином приводит к снижению абсолютной и относительной площади ожога, увеличению скорости эпителизации ожоговой поверхности. На 5-е сут обнаружено снижение содержания вторичных и конечных продуктов ПОЛ в изопропанольной фазе, на 10-е сутки - снижение вторичных продуктов ПОЛ в гептановой фазе, конечных продуктов ПОЛ в изопропанольной фазе липидного экстракта. Заключение. Полученные результаты демонстрируют ускоряющий репарацию кожи в очаге ТТ эффект МТ в составе дермальной пленки за счет его ПОЛ-ограничивающего действия, расширяют представления о мультитропных эффектах МТ в организме и являются предпосылкой для применения ДП с МТ в клинической практике. Background. Development and pathogenetic justification of new approaches for local therapy of thermal trauma (TT) is a relevant and in-demand issue. Of special interest are dermal films (DF) containing endogenous pleiotropic regulators of homeostasis. Melatonin (MT) is one of such regulators that is suggested to be protective in TT. The aim of this study was to evaluate the effect of MT in the original DF on indexes of repair and concentration of lipid peroxidation (LPO) products in the injured skin after experimental TT. Methods. Experiments were performed on 126 Wistar male rats. Grade IIIA TT with an area of 3.5% was modeled by immersing a section of interscapular skin in purified water at a temperature of 98-99oC for 12 s. MT formulated into DF (0.005 g/g) based on sodium carboxymethylcellulose was applied after TT daily for 5 days. The macroscopic picture, area and depth of the burn wound, and the wound epithelization rate were evaluated on days 5 and 10 after TT. Concentration of LPO products in the injured skin homogenate was measured by extraction spectrophotometry in heptane and isopropanol phases of the lipid extract. Results. The accumulation of secondary and final LPO products in the heptane and isopropanol phases of the lipid extract on days 5 and 10 was associated with the burn area. The use of the original DF with MT resulted in a decrease in the absolute and relative areas of the burn and an increase in the rate of burn surface epithelialization. On day 5, a decrease in the content of secondary and final LPO products in the isopropanol phase was observed, and on day 10 decreases in secondary peroxidation products in the heptane phase and end LPO products in the isopropanol phase were detected. Conclusion. The results of this study demonstrated that MT formulated into DF accelerates skin repair in the TT focus due to its LPO-limiting effect, expands the understanding of MT pleiotropic effect, and represents a prerequisite for the clinical use of DF with MT.

scholarly journals The Effectiveness of Local Application of Melatonin in the Original Dermal Film in Experimental Thermal Trauma

2021 ◽  
Vol 11 (4) ◽  
pp. 581-589
Author(s):  
M Osikov ◽  
A Ageeva ◽  
Yu Ageev ◽  
A Fedosov ◽  
K Nikushkina ◽  
...  
Keyword(s):  
Surface Area ◽  
Local Therapy ◽  
The Body ◽  
Local Application ◽  
Immunohistochemical Method ◽  
Burn Wound ◽  
Wound Area ◽  
Thermal Trauma ◽  
Male Wistar Rats ◽  
The Absolute

Background: The development and pathogenetic substantiation of the new agents used for local therapy of thermal trauma (TT) is an urgent problem in medicine. Melatonin (MT) is an endogenous factor of homeostasis regulation with pleiotropic potential. The aim of our study was to assess the morphology, expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF), indicators of repair, oxidative destruction of lipids in the skin lesion focus in the dynamics of experimental TT under the conditions of using the original dermal film (DF) with MT. Methods and Results: The experiment was performed on 104 male Wistar rats weighing 200-240 g. For modeling TT II degree according to ICD-10 a relative area of 3.5% of the body surface, an interscapular region isolated from the surrounding tissues, was immersed in distilled water at 98-99 °C for 12 sec. DF based on sodium carboxymethylcellulose with an area of 12 cm2 with MT at a concentration of 5 mg/g was applied daily for five days. The wound area and epithelialization rate were calculated. The content of MMP-9 and VEGF in the burn wound was assessed by an immunohistochemical method. In the homogenate of the burn wound, the content of LPO products was assessed. Morphological and biochemical studies were performed on Days 5, 10 and 20 after TT induction. With experimental TT from Day 5 to Day 20, the absolute area of the burn wound decreases by 35%, the rate of epithelialization increases, the number of neutrophils in the focus of thermal damage decreases, while the representation of lymphocytes, histiocytes, and fibroblasts increases; the expression of MMP-9 and VEGF increases; predominantly secondary and final LPO products in the heptane phase accumulate, the final products of LPO in the isopropanol phase of the lipid extract. The use of MT in the composition of DF daily for 5 days with experimental TT leads to a decrease in the area of the wound defect (by 46% of the original area on Day 20), an increase in the rate of its epithelialization, an increase in the content of lymphocytes and fibroblasts in the burn wound on Days 5, 10 and 20 of TT, a decrease in the representation of neutrophils and macrophages on Days 5 and 10, as well as an increase in VEGF expression on Days 5 and 10, MMP-9 - on Day 5 and a decrease in MMP-9 expression on Days 10 and 20 of TT. In addition, the use of MT in the composition of DF leads to a decrease in the content of predominantly secondary and end products of LPO in the heptane and isopropanol phases of the burn wound on Days 10 and 20 of TT. Correlation analysis revealed that a decrease in the burn surface area under a local application of MT occurs with an increase in the content of VEGF in the wound area and a decrease in the content of MMP-9 and secondary and final LPO products in the heptane phase and the isopropanol phase. On Day 20, there were direct moderate correlations between the absolute burn surface area, on one hand, and secondary and final LPO products, on the other, in the heptane phase (R=0.51, R=0,68; P<0.05) and the isopropanol phase (R=0.44, R=0.46; P<0.05), respectively. Conclusion: The results obtained expand the existing understanding of the role of changes in the expression of MMP-9 and VEGF in the pathogenesis of TT. We believe that the repair-stimulating effect of MT in the DF, which we established during TT at the preclinical stage, is associated with the LPO-limiting effect of MT and a change in the expression of MMP-9 and VEGF in the burn wound and is a prerequisite for further study of the mechanism of action and the effectiveness of MT application in clinical conditions in TT.

scholarly journals Electron microscopic changes of the testis germinal epithelium after an experimental thermal trauma in the application of cryo-lyophilized xenograft skin substrate

2018 ◽  
Vol 24 (4) ◽  
pp. 53-57
Author(s):  
K.S. Volkov ◽  
S.Yu. Muha
Keyword(s):  
Burn Injury ◽  
White Male ◽  
Male Rats ◽  
Germinal Epithelium ◽  
Seminiferous Tubules ◽  
Large Area ◽  
Burn Wound ◽  
Thermal Burn ◽  
Experimental Animals ◽  
Thermal Trauma

Deep, large area of thermal trauma of the skin leads to significant morphofunctional changes in organs in the composition of the burned organism. However, condition of the central organ of the male reproductive system - testicle after burns and, especially, in the treatment of thermally damaged areas of the skin remain poorly understood. The purpose of this study was to establish an ultrastructural re-organization of testis germinal epithelium cells in the stages of toxemia and septicotoxemia following an experimental thermal trauma when using xenograft skin substrate. The studies were carried out on 35 sexually mature white male rats, which were divided into three groups: 1 - intact animals (5 rats), 2 - animals with burn injury (15 rats), 3 - animals with burn injury, for which were used xenograft skin substrate (15 rats). The burn was applied under ketamine anesthesia with copper plates, heated in boiling water, on 1820% shaved body surface of animals. Early necrectomy of the damaged areas of skin was carried out 1 day after the thermal burn. The formed wounds were covered with cryo-lyophilized xenograft skin substrate. Experimental animals were decapitated at 7, 14 and 21 days of the experiment (early, late toxemia and septicotoxemia). The material sampling for electron microscopy was carried out in accordance with a generally accepted methodology. It is established that in the stage of early toxemia (7 days of experiment) there are adaptive-compensatory changes and signs of destruction of spermatogenic cells of testis. In the stages of late toxemia and septicotoxemia (14 and 21 days of the trial), significant destructive changes occur in all components of the seminiferous tubules of the organ. Electron microscopically found that the closure of the burn wound after the early necrectomy of cryo-lyophilized xenograft skin substrate in severe experimental burn injury in the early stages of the experiment significantly reduces the damage of testis germinal epithelium of experimental animals and activates regenerative processes. This contributes to a significant improvement in the ultrastructure of the components of the convoluted tubules of the organ in the late stages of the experiment.

scholarly journals Effect of erythropoietin on the content of lipid peroxidation products in lymphocytes in experimental thermal injury

2015 ◽  
Vol 96 (5) ◽  
pp. 849-853 ◽  
Author(s):  
M V Osikov ◽  
E V Simonyan ◽  
O T Saedgalina
Keyword(s):  
Lipid Peroxidation ◽  
Peripheral Blood ◽  
Thermal Injury ◽  
White Male ◽  
Peripheral Blood Lymphocytes ◽  
Lipid Extract ◽  
Male Rats ◽  
Diene Conjugates ◽  
Lipid Peroxidation Products ◽  
Blood Lymphocytes

Aim. To investigate the effect of different concentrations of erythropoietin on the content of lipid peroxidation products in lymphocytes isolated from the blood of rats with thermal injury. Methods. The study was performed on 22 white male rats. Thermal injury of IIIA degree on 4% of body surface area was simulated by immersion in water at a temperature of 98-99 °C. After 24 hours, blood lymphocytes were isolated and the content of the primary (diene conjugates), secondary (ketodienes and conjugated trienes) and final products (Schiff bases) of lipid peroxidation were determined spectrophotometrically. Erythropoietin was added to lymphocytes at concentrations of 0.01; 0.1 and 1 IU/ml. Results. It was found that 24 hours after thermal injury there were the accumulation of primary, secondary and final products of lipid peroxidation in isopropanol fraction of lipid extracts of peripheral blood lymphocytes. Addition of erythropoietin to the rat lymphocytes resulted in a controversial change in the content of lipid peroxidation products: an increase in the heptane fraction, decrease - in the isopropanol fraction of lipid extract of lymphocytes. In the heptane fraction erythropoietin (at concentrations of 0.01, 0.1, and 1 IU/ml) increased the content of primary, end (at a concentration of 0.1 IU/ml) and secondary (at a concentration of 1 IU/ml) lipid peroxidation products. In isopropanol fraction erythropoietin reduced the content of primary (at concentrations of 0.01, 0.1, and 1 IU/ml), final (at concentrations of 0.01 and 0.1 IU/ml) and secondary (at concentrations of 0.01 and 1 IU/ml) products of lipid peroxidation. Conclusion. It was found that there is an accumulation of lipid peroxidation products in the isopropanol fraction of lipid extract of lymphocytes isolated from peripheral blood of rats with thermal injury; erythropoietin application at concentrations of 0.01; 0.1 and 1 IU/ml increases the content of lipid peroxidation products in heptane fraction and decrease in the isopropanol fraction of lipid extract of lymphocytes.

Evaluating the Proposed Mechanism by Which Atorvastatin Can Protect Renal Tissue against Contrast Media: An Animal study

2019 ◽  
pp. 75-84
Keyword(s):  
Contrast Media ◽  
Kidney Injury ◽  
Saline Group ◽  
Pleiotropic Effect ◽  
Renal Tissue ◽  
Male Rats ◽  
Dependent Manner ◽  
Group 2 ◽  
Dose Dependent ◽  
Media Group

Contrast- induced nephropathy (CIN) is an elevation of serum creatinine of ≥ 0.5 mg/dL from baseline after two to three days of exposure to contrast substance if there is no other cause for acute kidney injury. Atorvastatin may protect normal kidney physiology from contrast- induced kidney injury by effects unrelated to hypolipidemia termed pleiotropic effect by decline of endothelin production, angiotensin system down regulation, and under expression of endothelial adhesion molecules. This study was conducted to assess the strategy by which atorvastatin can achieve protective effect for kidneys after exposure to contrast media in an animal model. A 40 male rats were distributed randomly into 4 groups; ten rats for each: group (1): given normal saline; group (2): CIN group given iopromide as contrast media; group (3): given atorvastatin (20mg/kg) and iopromide; and group (4): given atorvastatin (40mg/kg) and iopromide. Blood collected by cardiac puncture for detection of serum glutathione, malondialdehyde, matrix metalloproteinase-9, and interleukin-18. The results have shown a significant increase in inflammatory and oxidative stress markers in contrast media group, and significant reduction in these markers in atorvastatin treated groups, in a dose-dependent manner. As conclusion, atorvastatin mechanism for protection against CIN in a dose-dependent manner can mediate by anti-inflammatory and antioxidant effects.

Increased severity of alcoholic liver injury in female rats: role of oxidative stress, endotoxin, and chemokines

2001 ◽  
Vol 281 (6) ◽  
pp. G1348-G1356 ◽  
Author(s):  
Amin A. Nanji ◽  
Kalle Jokelainen ◽  
Maryam Fotouhinia ◽  
Amir Rahemtulla ◽  
Peter Thomas ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Liver Injury ◽  
Fish Oil ◽  
Nonheme Iron ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Alcoholic Liver Injury ◽  
Tnf Α ◽  
Cox 2

Alcoholic liver injury is more severe and rapidly developing in women than men. To evaluate the reason(s) for these gender-related differences, we determined whether pathogenic mechanisms important in alcoholic liver injury in male rats were further upregulated in female rats. Male and age-matched female rats (7/group) were fed ethanol and a diet containing fish oil for 4 wk by intragastric infusion. Dextrose isocalorically replaced ethanol in control rats. We analyzed liver histopathology, lipid peroxidation, cytochrome P-450 (CYP)2E1 activity, nonheme iron, endotoxin, nuclear factor-κB (NF-κB) activation, and mRNA levels of cyclooxygenase-1 (COX-1) and COX-2, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2). Alcohol-induced liver injury was more severe in female vs. male rats. Female rats had higher endotoxin, lipid peroxidation, and nonheme iron levels and increased NF-κB activation and upregulation of the chemokines MCP-1 and MIP-2. CYP2E1 activity and TNF-α and COX-2 levels were similar in male and female rats. Remarkably, female rats fed fish oil and dextrose also showed necrosis and inflammation. Our findings in ethanol-fed rats suggest that increased endotoxemia and lipid peroxidation in females stimulate NF-κB activation and chemokine production, enhancing liver injury. TNF-α and COX-2 upregulation are probably important in causing liver injury but do not explain gender-related differences.

scholarly journals Effects of Sleep Deprivation, Nicotine, and Selenium on Wound Healing in Rats

2017 ◽  
Author(s):  
Kenan Gümüstekin ◽  
Bedri Seven ◽  
Nezihe Karabulut ◽  
Ömer Aktas ◽  
Nesrin Gürsan ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Wound Healing ◽  
Sleep Deprivation ◽  
Immunoglobulin G ◽  
Male Rats ◽  
Polymorphonuclear Leucocytes ◽  
Sprague Dawley ◽  
Accelerate Wound Healing ◽  
Pathological Analysis

Effects of sleep deprivation (SD), nicotine, and selenium (Se) on woundhealing were studied in 50 male rats (Sprague-Dawley strain). Fullskin-thickness burns were produced in animals. Then, SD, nicotine, andSe administrations were applied to animals in different groups. Woundhealing was assessed by pathological analysis of wound by countingfibroblasts, capillary vessels, polymorphonuclear leucocytes (PNLs), andby measuring radiolabeled immunoglobulin G (IgG) amount in woundarea by radio-pharmaceutical and immunoscintigraphic procedures. Thenumber of fibroblasts and capillary vessels were higher in control andSe groups than in sleep deprivation and nicotine groups, and the numberof PNLs and the radiolabeled polyvalent IgG levels were higher inSD and nicotine groups than in control and Se groups. The resultssuggest that SD and nicotine may delay wound healing and that Sesupplementation may accelerate wound healing by preventing nicotineinducedoxidative stress and lipid peroxidation.

scholarly journals Preclinical Study on the Ameliorating Effect of L-Ascorbic Acid for the Oxidative Stress of Caused by Chronic Administration of Organic Nitrates in Cardiovascular Diseases

2021 ◽  
Author(s):  
Ahmed M Hamdan ◽  
Zuhair M. Mohammedsaleh ◽  
Aalaa Aboelnour ◽  
Sherif M.H. Elkhannishi
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Chronic Administration ◽  
Stress Factors ◽  
Male Rats ◽  
Oxidative Stress Marker ◽  
Organic Nitrates ◽  
Dependent Manner ◽  
Dose Dependent

Abstract PurposeThe therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. The principal objective of our research is to explain the ameliorating effect of L-ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs. MethodsWe studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered ISMN. Afterwards, we evaluated the role of L-ascorbic acid against these biochemical changes. ResultsChronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in myocardium muscles in a dose dependent manner. Meanwhile, such exposure caused decline in the enzymatic effect of superoxide dismutase (SOD), glutathione (GSH) and catalase activity (CAT) accompanied with a decrease of in the level of mitochondrial oxidative stress marker (nrf2) in myocardium muscles and decrease in the serum iron and total iron binding capacity (TIBC) in a dose dependent manner. Concomitant treatment with L-ascorbic acid significantly diminished these changes for all examined parameters.ConclusionChronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to generation of reactive oxygen species. Using vitamin C can effectively ameliorate such intoxication to overcome the nitrate tolerance.

scholarly journals NADPH Oxidase Activity and Reactive Oxygen Species Production in Brain and Kidney of Adult Male Hypertensive Ren-2 Transgenic Rats

2015 ◽  
pp. 849-856 ◽  
Author(s):  
M. VOKURKOVÁ ◽  
H. RAUCHOVÁ ◽  
L. ŘEZÁČOVÁ ◽  
I. VANĚČKOVÁ ◽  
J. ZICHA
Keyword(s):  
Reactive Oxygen Species ◽  
Lipid Peroxidation ◽  
Nadph Oxidase ◽  
Medulla Oblongata ◽  
Renal Cortex ◽  
Reactive Oxygen ◽  
Male Rats ◽  
Ventrolateral Medulla ◽  
Oxygen Species ◽  
O2 Production

Hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play an important role in brain control of blood pressure (BP). One of the important mechanisms involved in the pathogenesis of hypertension is the elevation of reactive oxygen species (ROS) production by nicotine adenine dinucleotide phosphate (NADPH) oxidase. The aim of our present study was to investigate NADPH oxidase-mediated superoxide (O2-) production and to search for the signs of lipid peroxidation in hypothalamus and medulla oblongata as well as in renal medulla and cortex of hypertensive male rats transgenic for the murine Ren-2 renin gene (Ren-2 TGR) and their age-matched normotensive controls ‒ Hannover Sprague Dawley rats (HanSD). We found no difference in the activity of NADPH oxidase measured as a lucigenin-mediated O2- production in the hypothalamus and medulla oblongata. However, we observed significantly elevated NADPH oxidase in both renal cortex and medulla of Ren-2 TGR compared with HanSD. Losartan (LOS) treatment (10 mg/kg body weight/day) for 2 months (Ren-2 TGR+LOS) did not change NADPH oxidase-dependent O2- production in the kidney. We detected significantly elevated indirect markers of lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS) in Ren-2 TGR, while they were significantly decreased in Ren-2 TGR+LOS. In conclusion, the present study shows increased NADPH oxidase activities in renal cortex and medulla with significantly increased TBARS in renal cortex. No significant changes of NADPH oxidase and markers of lipid peroxidation were detected in the studied brain regions.

Thallium Induced Changes in Behavioral Patterns: Correlation With Altered Lipid Peroxidation and Lysosomal Enzyme Activity in Brain Regions of Male Rats

1985 ◽  
Vol 1 (1) ◽  
pp. 81-98 ◽  
Author(s):  
David R. Brown ◽  
Barbara G. Callahan ◽  
Mark A. Cleaves ◽  
Robert A. Schatz
Keyword(s):  
Lipid Peroxidation ◽  
Lysosomal Enzyme ◽  
Brain Regions ◽  
Male Rats ◽  
Patterns Of Behavior ◽  
Low Levels ◽  
Behavioral Sequelae ◽  
Human Poisoning ◽  
And Function ◽  
Induced Changes

The effects of exposures to low levels of heavy metals is a complex and serious problem. Thallium is a metal which produces behavioral sequelae in human poisoning and is potentially hazardous with low level exposures. A test battery is presented which utilizes biochemical and behavioral testing to assess the effects of low levels of thallium on central nervous system chemistry and function in rats. The doses of thallium used (4 and 8 mg/kg) produced no overt signs of behavioral toxicity but did produce dose-related increases in lipid peroxidation and activation of the lysosomal enzyme beta-galactosidase in selected brain regions. At these dose levels, thallium also selectively altered the patterns of behavior. The study suggests that the target regions of thallium in the brain include the cortex, the cerebellum and the brainstem. The dose-response relationships, found for certain pairs of behavioral acts, were correlated with biochemical changes in one or more brain regions.

scholarly journals Organ-Specific Oxidative Events under Restrictive Versus Full Reperfusion Following Hemorrhagic Traumatic Shock in Rats

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2195
Author(s):  
Carina Penzenstadler ◽  
Anna Zifko ◽  
Mohammad Jafarmadar ◽  
Janin Schulte ◽  
Joachim Struck ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Thiobarbituric Acid ◽  
Traumatic Shock ◽  
Male Rats ◽  
Resonance Spectroscopy ◽  
Stress Reactions ◽  
Paramagnetic Resonance ◽  
Early Reperfusion ◽  
Ros Formation

Background aim: Reperfusion after hemorrhagic traumatic shock (HTS) is often associated with complications that are partly ascribed to the formation of reactive oxygen species (ROS). The aim of our study was to compare the effects of restrictive reperfusion (RR) to rapid full reperfusion (FR) on ROS formation and/or oxidative events. Materials and methods: Anesthetized male rats were randomly subjected to HTS followed by FR (75 mL/kg/h) or RR (30 mL/kg/h for 40 min, followed by 75 mL/kg/h) with Ringer’s solution (n = 8/group). Compartment-specific ROS formation was determined by infusion of ROS scavenger 1-hydroxy-3-carboxy-2,2,5,5-tetramethyl-pyrrolidine hydrochloride (CP-H) during resuscitation, followed by electron paramagnetic resonance spectroscopy. Sham-operated animals (n = 8) served as controls. The experiment was terminated 100 min post-shock. Results: Mean arterial pressure was significantly higher in the FR compared to the RR group during early reperfusion. Only RR animals, not FR animals, showed significantly higher ROS concentrations in erythrocytes (1951 ± 420 vs. 724 ± 75 AU) and in liver (474 ± 57 vs. 261 ± 21 AU) compared to sham controls. This was accompanied by elevated alanine aminotransferase and creatinine levels in RR animals compared to both shams and FR animals, while lipid peroxidation products (thiobarbituric acid reactive substances) were significantly increased only in the kidney in the FR group (p < 0.05). RR animals showed significantly higher plasma peroxiredoxin-4 values when compared to the FR group (20 ± 2 vs. 14 ± 0.5 RLU). Conclusion: Restrictive reperfusion after HTS is associated with increased ROS formation in erythrocytes and liver compared to sham controls. Moreover, the restrictive reperfusion is associated with a more pronounced injury to the liver and kidney, which is likely mediated by other than lipid peroxidation process and/or oxidative stress reactions.

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