Целью настоящего исследования служило определение корреляционных связей между показателями состояния оксидантно-антиоксидантного напряжения в крови экспериментальных животных, а также содержанием билирубина и активностью ферментов в условиях экспериментальной механической желтухи. Исследования проведены на 84 половозрелых крысах-самцах линии Вистар, массой 180-230 г. Животные были распределены на 4 группы: интактные (n=12), контроль (n=24), L-лизина эсцинат (0,5 мг/кг, n=24) и Глутаргин (40 мг/кг, n=24). Выделение и перевязка общего желчного протока проводились ниже конфлюэнса в условиях общей анестезии. Исследуемые препараты вводились 1 раз в сутки, внутрибрюшинно. Оценку эффективности проводимой терапии проводили на 4 и 10-е сутки эксперимента. Содержание малонового диальдегида (МДА), альдегид- (АФГ) и кетонфенилгидразонов (КФГ), билирубина, а также активность супероксиддисмутазы (СОД), каталазы, аспартат- (АлАТ) и аланинаминотрансферазы (АсАТ) в крови определяли с использованием общепринятых методик. Проведенными исследованиями определены коррелятивные связи между традиционными показателями (билирубин, АсАТ, АлАТ) и показателями, характеризующими состояние оксидантно-антиоксидантного напряжения (МДА, АФГ, КФГ, СОД, каталаза). Установлена высокая степень корреляции между ними. Результаты позволяют опосредованно оценивать интенсивность процессов окислительного метаболизма в печени, что может быть использовано в клинике для оценки степени тяжести больных с прогрессирующей механической желтухой. The aim of this study was to determine the correlations between markers of oxidant-antioxidant stress in the blood of experimental animals, as well as the content of bilirubin and activity of enzymes in experimental obstructive jaundice. Studies were conducted on 84 adult male Wistar rats (180-230 g). Animals were divided into 4 groups: intact (n = 12), control (n = 24), L-lysine escinate (0,5 mg/kg, n = 24) and glutargin (40 mg/kg, n = 24). The isolation and ligation of the common bile duct below confluence was carried out under general anesthesia. The test preparations were administered 1 time per day, intraperitoneally. Evaluation of the treatment efficacy was carried out on 4th and 10th day of the study. The content of malonic dialdehyde (MDA), aldehyde- (APH) and ketone-phenylhydrazones (CPH), bilirubin and the activity of superoxide dismutase (SOD), catalase, aspartate aminotransferase (ALT) and alanine aminotransferase (AST) in the blood were determined using conventional techniques. The correlation links between common markers (bilirubin, AST, ALT) and indicators characterizing oxidant-antioxidant stress (MDA, APH, CPH, SOD, catalase) were determined in the study. High rate of correlation between them was established. The results allow to evaluate indirectly the intensity of oxidative metabolism processes in the liver, which can be used in clinical practice to assess the severity degree of the patients with progressive obstructive jaundice.
Исследования посвящены изучению влияния цитиколина, фенилпирацетама, пентоксифиллина и N-фенилацетил-L-пролилглицина на мнестические процессы и функциональное состояние митохондрий в неокортексе крыс c аллоксановой гипергликемией. Оценку влияния препаратов на мнестические процессы проводили с помощью условной реакции пассивного избегания в темно-светлой камере. Регистрировали латентный период и число животных с амнезией навыка на 6 и 20 сут введения препаратов. Функциональное состояние митохондрий оценивали по открытию митохондриальной поры и митохондриальному трансмембранному потенциалу (Ψ) на 20 сут. Установлено, что курсовое применение фенилпирацетама, цитиколина и, в меньшей степени, N-фенилацетил-L-пролилглицина, но не пентоксифиллина, улучшало процессы обучения и хранения условного навыка. При этом ноотропная активность изученных средств была сопоставима с их влиянием на функциональное состояние митохондрий нейронов неокортекса крыс с хронической гипергликемией. Степень митопротективной активности (предупреждение открывания митохондриальной циклоспорин-А-чувствительной поры и восстановление митохондриального трансмембранного потенциала) была наибольшей у цитиколина и фенилпирацетама, а наименьшей — у пентоксифиллина.
Aim: determine morphometric and ultrastructural features of blood microcirculation in hippocampus of rats with alloxan diabetes under experimental therapy with citicoline.Materials and methods. The research was carried out on 48 white male Wistar rats (250-300 g) randomized in 3 groups by 16 animals: I – intact (distilled water, intragastrically); II – animals with diabetes (distilled water, intragastrically); III – animals with diabetes + citicoline (500 mg/kg, intragastrically). Diabetes was reproduced by single subcutaneous injection of alloxan monohydrate (150 mg/kg). Blood glucose level was determined on the 11th day after administration of alloxan using a glucometer. Citicoline and distilled water were introduced once a day during 20 days starting from the 11th day after administration of alloxan. In morpho-functional study of hippocampal CA1-zone neurons the histological sections were deparaffinized and dyed with gallocyanin-chrome alum by Einarson for specific detection of RNA. Pictures were received with a microscope Axioskop (Zeiss, Germany). Using a computer-based picture analysis system VIDAS-386 (Kontron Elektronik, Germany) the density of endothelial nuclei, the nucleus area and the concentration of RNA in the nucleus were determined. The study of ultrastructural changes of blood microcirculation in hippocampus was carried out using transmission electron microscope PEM-100-01 («SELMI», Ukraine) by standard procedure and in accordance with common standards. Statistical difference between the groups were assessed by non-parametric Mann-Whitney U-test.Results. It has been established that citicoline contributed to recovery of proliferative activity of endothelium in vascular bed of hippocampus manifested with increase of endothelial nuclei density, their area and levels of nuclear RNA by 19,4% (p < 0,001), 17,2% (p < 0,05) and 25,8% (p < 0,01). Simultaneously it has been determined that hematoencephalic barrier damage in hippocampus of rats under administration of citicoline were less expressed or virtually absent.Conclusion. Thus, stimulation of revascularization processes, optimization of metabolic processes and also lack of pronounced changes in microcirculatory bed in hippocampus of rats with alloxan diabetes are the evidence of expressed endothelium-protective activity of citicoline
Aim of the study: to determine relationship between antiamnesic properties of piracetam and phenylpiracetam and their influence on the processes of proteins oxidative modification and production of nitric oxide in brain cortex of rats with alloxan-induced hyperglycemia. Diabetes mellitus was induced in rats by a single administration of alloxan monohydrate (150 mg/kg). Antiamnesic activity of piracetam (500 mg/kg) and phenylpiracetam (100 mg/kg) was estimated in conditions of hyoscine-induced amnesia (0,8 mg/kg) in the passive avoidance test. The drugs were administered intragastrically once per day during 20 days from the 11th day after alloxan injection. On the 30th day the level of aldehydephenylhydrazones (APH) and ketonphenylhydrazones (KPH), total level of nitrite and nitrate (NOx) in homogenates of cerebral cortex were determined by spectrophotometric assay. It has been found that long-term hyperglycemia potentiates the amnesic properties of hyoscine and is accompanied by increased intensity of proteins oxidative modification and synthesis of nitric oxide in the brain cortex. Phenylpiracetam possesses greater antiamnesic potential as compared to piracetam. Also it significantly reduces the amount of early (APH) and late (KPH) markers of protein molecules degradation and decreases the level of nitric oxide stable metabolites. Conclusion. These results reveal new mechanisms of neuroprotective properties of the studied drugs, particularly in diabetes mellitus.
The effects of nootropic drugs (noopept, pentoxifylline, piracetam, pramiracetam, Ginkgo biloba extract, entrop, cerebrocurin and citicoline) on platelet aggregation in rats with experimental diabetes have been studied. It is established that all these drugs exhibit an inhibitory action of various degrees against platelet hyperreactivity under conditions of chronic hyperglycemia. The maximum universality of the antiaggregatory action is characteristic of pramiracetam, entrop and Ginkgo biloba extract.