Liposomal form of dexamethasone in the correction of experimental acute lung injury

Objective. To investigate the possibility of pharmacological correction of acute lung injury of aspiration genesis with a liposomal form of dexamethasone in experiment. Materials and methods. For the experiment, simple liposomes were prepared from phosphatidylcholine and cholesterol with an average size of 320±50 nm and a dexamethasone concentration of 2.98±0.02 mg/ml. The study used outbred white rats, divided into four groups of 16 animals. 1st group Control (without experimental therapy), 2nd group - Experiment 1, where a solution of dexamethasone was injected intravenously at a dose of 6 mg/kg, 3rd group - Experiment 2, where an intravenous combination of dexamethasone solution (6 mg/kg) and hypertonic (7.5%) NaCl solution was administered once, and group 4 - Experiment 3, where liposomes with dexamethasone (6 mg/kg) were injected intravenously once in hypertensive (7.5%) NaCl solution. The main functional parameters of the animals (heart rate, blood pressure, saturation of hemoglobin with oxygen, partial pressure of blood oxygen and respiration rate) were subject to analysis. Functional parameters were analyzed before modeling acute lung injury and after 5 min, 1, 4, 24 hours, and 6 days. At the end of the experiment (day 6) the degree of pulmonary edema and histological signs of acute lung injury were assessed. Morphology was assessed quantitatively in each group. Results. The study found that liposomal dexamethasone in hypertonic NaCl solution, when administered intravenously, was more effective than aqueous dexamethasone solution in correcting functional impairment in acute lung injury. The combination of hypertonic sodium chloride solution with dexamethasone more markedly increases blood pressure and reduces the degree of pulmonary oedema. In acidine pepsin aspiration, liposomal dexamethasone in hypertonic NaCl solution most effectively increased animal survival. Conclusion. Compared with dexamethasone in hypertonic NaCl solution, liposomal dexamethasone is more effective in increasing animal survival and protecting lung tissue from aspiration damage by acidine pepsin.

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СУБМІКРОСКОПІЧНІ ЗМІНИ КОМПОНЕНТІВ АЕРОГЕМАТИЧНОГО БАР’ЄРУ РЕСПІРАТОРНОГО ВІДДІЛУ ЛЕГЕНЬ ЩУРІВ У РАННІ ТЕРМІНИ ПІСЛЯ ГОСТРОГО УРАЖЕННЯ ХЛОРИДНОЮ КИСЛОТОЮ

Вісник наукових досліджень ◽

10.11603/2415-8798.2018.2.9154 ◽

2018 ◽

Author(s):

V. O. Beskyy ◽

Z. M. Nebesna ◽

M. I. Marushchak ◽

L. A. Hryshchuk

Keyword(s):

Acute Lung Injury ◽

Hydrochloric Acid ◽

Lung Injury ◽

Early Period ◽

Alveolar Epithelium ◽

Male Rats ◽

Control Group ◽

Ultrastructural Organization ◽

Type I ◽

White Rats

Submicroscopic studies of the respiratory part of the lungs after 2 and 6 hours after the experimental acute lung injury with hydrochloric acid established adaptive-compensatory and destructive changes in the components of the air-blood barrier.The aim of the study – to learn submicroscopic changes in the components of the air-blood barrier of the lungs in the early period after acute lung injury.Materials and Methods. The experiments were carried out on 30 white mature non-linear male rats weighing 200–220 g. The animals were divided into 3 groups: 1 – control group, 2 – hydrochloric acid damage after 2 hours, 3 – hydrochloric acid damage after 6 hour.Results and Discussion. In an experiment on mature white rats, a study was made of the submicroscopic state of the components of the air-blood barrier in the early periods after acute lung injury. It has been established that adaptive-compensatory and initial destructive changes of the alveolar epithelium and the walls of the hemocapillary take place at 2 o'clock in the experiment. The cytoplasm of respiratory epitheliocytes during this period of the experiment was focal-edematous and enlightened, organelles were destructively altered. For alveolocytes of type I, there was a significant swelling and clarification of the cytoplasm. During this period of the experiment, an increased number of actively phagocytizing macrophages appeared, which acquired a rounded shape, clearly contoured membranes of the cariolema, their invaginations were determined, and in the karyoplasm euchromatin predominated. In alveolocytes of type II, after 6 hours, the progression of destructive changes was established. For which there were peculiarity hypertrophied nuclei with deep invagination of the cariolema, in which there were few nuclear pores, locally expanded perinuclear space. In the edematous cytoplasm, organelles were found to be destructively altered.Conclusions. Acute damage to the lungs leads to a disruption of the ultrastructural organization of the air-blood barrier. Established adaptive-compensatory processes and signs of destructive changes in the alveolar epithelium and the walls of hemocapillaries, which leads to deterioration of gas-exchange processes in the lungs.

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THE MORPHOLOGY OF THE LUNGS AT THE EXPERIMENTAL ACUTE INJURY AND ITS PHARMACOCORRECTION

MORPHOLOGICAL NEWSLETTER ◽

10.20340/mv-mn.2020.28(2):64-73 ◽

2020 ◽

Vol 28 (2) ◽

pp. 64-73

Author(s):

Oleg A. Kulikov ◽

Vladimir P. Balashov ◽

Valentin P. Ageev ◽

Elena V. Semenova ◽

Vasilisa I. Shlyapkina ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Quantitative Assessment ◽

Acute Injury ◽

Control Group ◽

Liposomal Form ◽

Experimental Animals ◽

Pharmacological Correction ◽

The Moment ◽

The Impact

The study of lung morphology under the influence of various environmental factors is of great interest for various areas of medicine and biology. The study of pathological changes in the respiratory part of the lung of rats with aspiration acute injury and the action of pharmacological correction was carried out. Acetone was used as a damaging agent, and HyperHAES was used as a means of pharmacological correction, containing 7.2% NaCl solution in combination with 6% hydroxyethyl starch, as well as a liposomal form of N-acetylcysteine, which was administered to experimental animals once intravenously after induction of acute lung injury. The control group of animals received antibiotic therapy. The staining of the slides was carried out using hematoxylin and eosin. A quantitative assessment of the histological signs of lung tissue damage was carried out. As a result of the study of preparations of the lungs, the degree of pulmonary edema was established, as well as the anti-edema effect of pharmacological corrections. On the 6th day of the experiment, the anti-edematous effect was retained only after the introduction of N-acetylcysteine. Histological examination of the lungs showed generalized destruction of the organ architectonics in response to the impact of a damaging factor and its reduction under the influence of pharmacological corrections. In the control group, the signs of acute lung injury were most extensive. One day after the administration of the HyperHAEC solution, there were no hemorrhages in the histological picture of the lungs. In a quantitative assessment of the histological signs of acute lung injury, it was shown that the maximum positive effect from the administration of HyperHAES develops 24 hours after application. N-acetylcysteine primarily led to a decrease in leukocyte infiltration and prevented the development of a suppurative process. The lung-protective effect of N-acetylcysteine was realized in 24 hours from the moment of administration and persisted until the 6th day of the experiment. The use of pharmacological correction agents in acute lung injury was reflected in the picture of the lethality of the experimental animals. When HyperHAES was applied, 37.5% of animals died by day 6, in the group with N-acetylcysteine - 28.6%, while in the control group all animals died.

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The features of the course of virus-associated acute lung injury in mice with induced immunosuppression

Medical academic journal ◽

10.17816/maj77325 ◽

2021 ◽

Vol 21 (3) ◽

pp. 75-80

Author(s):

Andrey G. Aleksandrov

Keyword(s):

Influenza Virus ◽

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Cytokines ◽

Influenza Infection ◽

Lung Damage ◽

Experimental Therapy ◽

Blood Oxygen ◽

Blood Oxygen Saturation ◽

Pro Inflammatory Cytokines

BACKGROUND: Among all groups of patients with virus-associated acute lung injury with influenza infection, the most severe course is observed in patients with immunosuppression. In this case, despite the studied mechanism of the course of combined pathology, the question of therapy in this group of patients remains unclear. AIM: To study the features of the course of acute lung injury in influenza infection with secondary immunosuppression in an experiment for the possibility of searching for experimental therapy for this combined pathology. MATERIALS AND METHODS: The study was performed on 115 outbred female mice. The mouse-adapted pandemic influenza virus A/California/7/09MA (H1N1)pdm09 was used for modeling viral acute lung injury. Experimental immunosuppression was reproduced by administration of methotrexate (1.25 mg/kg intraperitoneally, once every 3 days during 3 weeks before infection). During the experiment, mortality, blood oxygen saturation, the concentration of pro-inflammatory cytokines in the lungs, and the severity of lung injury were measured. RESULTS: The presence of experimental immunosuppression led to an exacerbation of acute lung injury in infected animals in terms of mortality and lung damage. Changes in the dynamics of proinflammatory cytokines (TNF-, IL-6, IL-1) in the lungs were observed during acute lung injury. Retarded recovery of the lungs functional activity was noted. CONCLUSIONS: The experimental immunosuppression contributed to the exacerbation of acute lung injury and to an increase in the duration of the pathology. These changes could be associated with an altered process of elimination of the pathogen. The reproduced model of combined pathology was used for searching a therapy for these complications.

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Efficacy of liposomal dosage forms and hyperosmolar salines in experimental pharmacotherapy of acute lung injury

Research Results in Pharmacology ◽

10.3897/rrpharmacology.5.35529 ◽

2019 ◽

Vol 5 (2) ◽

pp. 23-41

Author(s):

Oleg A. Kulikov ◽

Valentin P. Ageev ◽

Elena E. Marochkina ◽

Irina S. Dolgacheva ◽

Olga V. Minayeva ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Intravenous Administration ◽

Fluorescence Intensity ◽

Average Diameter ◽

Laboratory Animals ◽

Experimental Therapy ◽

Hypertonic Solutions ◽

Calibration Dependence ◽

Liposomal Drugs

Introduction: Hypertonic sodium chloride solutions and liposomal drugs with pulmotropic effect are of great interest for the treatment of acute lung injury (ALI). The results of the studies on the efficacy of hypertonic solutions and liposomes in ALI treatment are currently controversial.Materials and methods: For the experiment, liposomes with dexamethasone, N-acetylcysteine (NAC), aprotinin and dye Cyanine-7 (Cy-7) were obtained. A liposome analysis was performed by means of spectrophotometry. ALI was modeled in rats by the administration of the damaging agents into the trachea. The experimental agents were injected once intravenously after the modeling of ALI. For experimental therapy used liposomal agents, 7.5% hypertonic saline (HS) and HyperHAES solutions in the respective groups. The efficacy of the therapy was assessed by the survival of animals, functional indicators of the cardiovascular and respiratory systems, and by the lung-body ratio. The biodistribution of liposomes after intravenous administration was investigated in mice through using a fluorescent dye Cy-7. The biodistribution of liposomes with Cy-7 was assessed using bioimaging according to the fluorescence intensity of internal organs (lungs, liver, and kidneys) and blood, expressed as dye concentration according to the calibration dependence of dye concentrarion on fluorescence intensity.Results and discussion: All the studied liposomal drugs were effective for the pharmacological correction of ALI. Hypertonic solutions, unlike liposomal drugs, were less likely to prevent the development of pulmonary edema. All the studied therapeutic agents increased the survival rate of the laboratory animals with ALI. The most effective experimental agent was liposomal dexamethasone. The use of drugs in form of simple liposomes with average diameter of 350 nm provided for a higher concentration of the drug in the lungs within the first 40 minutes after intravenous administration.Conclusion: Intravenous administration of liposomal forms is promising for the pharmacotherapy of acute lung injury.

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