flavin-mononucleotide and Disease-Models--Animal

Involutional changes in the cerebral cortex substantially affect the activity of the cortex itself and the function of target organs. This necessitates pharmacological correction of age-related diseases, primarily a high level of cell death.. To investigate the role of cytoflavin in mechanisms for the apoptotic regulation of cerebral cortical cells during physiological and pathological aging (in the presence of HER-2/neu overexpression).. HER-2/neu transgenic mice were used; wild-type FVB/N mice served as controls. The levels of apoptosis (TUNEL) and the expression of its associated proteins (p53, CD95, Mcl-1, p-AKT, and p-ERK) (Western blotting) were estimated in the sensorimotor cortex.. Activation of fundamental AKT and ERK survival pathways promotes a low level of cell death in young FVB/N mice; the extrinsic receptor mechanism of apoptosis is observed to be initiated by aging. The high p-AKT levels in the cortical cells provide suppressed cell death in transgenic mice regardless of their age. After cytoflavin administration, the old wild-type mice show a lower level of apoptosis in the cortical neurons apparently due to the increased expression of the anti-apoptotic protein Mcl-1, while the old transgenic mice exhibited suppression of the AKT and ERK survival pathways and, accordingly, activation of the extrinsic receptor and p53-dependent apoptosis pathways.. Thus, cytoflavin exerts a pronounced neuroprotective effect during physiological and accelerated aging, while its effect on the level of neuronal apoptosis is ambiguous and depends on the genetic line of animals. So, this is a moderate stimulation of apoptosis when its level is low in HER-2/neu mice with a high level of carcinogenesis, as well as a decrease in the high level of apoptosis in old wild-type animals, which prevents neurodegeneration.. Как известно, инволюционные изменения коры головного мозга значительно влияют на активность самой коры и функции органов-мишеней. Это вызывает необходимость фармакологической коррекции зависимой от возраста патологии, в первую очередь высокого уровня клеточной гибели. Цель исследования - исследовать роль цитофлавина в механизмах регуляции апоптоза клеток коры головного мозга при физиологическом и патологическом старении (в условиях сверхэкспрессии HER-2/neu). Материал и методы. Использованы трансгенные мыши линии HER-2/neu, контроль - мыши дикого типа FVB/N. В сенсомоторной зоне коры головного мозга оценивали уровень апоптоза (TUNEL), содержание апоптоз-ассоциированных белков (p53, CD95, Mcl-1, р-AKT, p-ERК) (вестерн-блоттинг). Результаты. У молодых мышей FVB/N активация основных путей выживания AKT и ERK способствует низкому уровню гибели клеток, при старении наблюдается инициация внешнерецепторного механизма апоптоза. У трансгенных мышей вне зависимости от возраста высокое содержание p-AKT в клетках коры обеспечивает подавление клеточной смерти. После введения цитофлавина у старых мышей дикого типа снижается уровень апоптоза нейронов коры, очевидно, вследствие повышения экспрессии антиапоптотического белка Mcl-1. У старых трансгенных мышей после введения цитофлавина наблюдается супрессия путей выживания AKT и ERK и соответственно активация внешнерецепторного и р53-зависимого путей апоптоза. Выводы. Таким образом, цитофлавин оказывает выраженное нейропротективное действие при физиологическом и ускоренном старении, при этом влияние его на уровень апоптоза нейронов неоднозначно и зависит от генетической линии животных. Так, это умеренная стимуляция апоптоза в случае низкого его уровня у HER-2/neu-мышей с высоким уровнем канцерогенеза и уменьшение высокого уровня апоптоза у старых животных дикого типа, что предупреждает нейродегенерацию.

Topics: Aging; Animals; Apoptosis; Cerebral Cortex; Disease Models, Animal; Drug Combinations; Female; Flavin Mononucleotide; Inosine Diphosphate; Mice; Niacinamide; Succinates

Microemulsions are widely studied as potential ocular drug delivery vehicles. In the present study we show the versatility of possible use microemulsions as ocular delivery vehicle. The ME is loaded with a hydrophilic drug, riboflavin phosphate (RFP) and a lipophilic, docosahexaenoic acid in triglyceride form (TG-DHA), each separately. These drugs treat keratoconus and dry eye syndrome, respectively. The advantage of using ME loaded with RFP is in overcoming eye epithelium debridement during collagen cross-linking therapy for treatment of keratoconus. ME loaded with lipophilic TG-DHA provides convenient dosage in liquid aqueous form of administration of highly lipophilic TG-DHA, which is known as a protective molecule in dry eye syndrome. The capability of RFP-loaded MEs was demonstrated in terms of improvement of biomechanical strength of the rabbit cornea, as a result of successful penetration of RFP through the intact epithelium. TG-DHA-loaded microemulsion applied topically onto an eye with induced dry eye syndrome showed the significant relief of the dry eye condition.

Topics: Animals; Biomechanical Phenomena; Collagen; Disease Models, Animal; Docosahexaenoic Acids; Drug Delivery Systems; Dry Eye Syndromes; Emulsions; Epithelium, Corneal; Flavin Mononucleotide; Humans; Hydrophobic and Hydrophilic Interactions; Keratoconus; Male; Permeability; Rabbits; Triglycerides; Ultraviolet Rays

Ischemic brain injury is characterized by 2 temporally distinct but interrelated phases: ischemia (primary energy failure) and reperfusion (secondary energy failure). Loss of cerebral blood flow leads to decreased oxygen levels and energy crisis in the ischemic area, initiating a sequence of pathophysiological events that after reoxygenation lead to ischemia/reperfusion (I/R) brain damage. Mitochondrial impairment and oxidative stress are known to be early events in I/R injury. However, the biochemical mechanisms of mitochondria damage in I/R are not completely understood.. We used a mouse model of transient focal cerebral ischemia to investigate acute I/R-induced changes of mitochondrial function, focusing on mechanisms of primary and secondary energy failure.. Ischemia induced a reversible loss of flavin mononucleotide from mitochondrial complex I leading to a transient decrease in its enzymatic activity, which is rapidly reversed on reoxygenation. Reestablishing blood flow led to a reversible oxidative modification of mitochondrial complex I thiol residues and inhibition of the enzyme. Administration of glutathione-ethyl ester at the onset of reperfusion prevented the decline of complex I activity and was associated with smaller infarct size and improved neurological outcome, suggesting that decreased oxidation of complex I thiols during I/R-induced oxidative stress may contribute to the neuroprotective effect of glutathione ester.. Our results unveil a key role of mitochondrial complex I in the development of I/R brain injury and provide the mechanistic basis for the well-established mitochondrial dysfunction caused by I/R. Targeting the functional integrity of complex I in the early phase of reperfusion may provide a novel therapeutic strategy to prevent tissue injury after stroke.

Topics: Animals; Brain; Brain Ischemia; Cerebrovascular Circulation; Citrate (si)-Synthase; Disease Models, Animal; Electron Transport Complex I; Energy Metabolism; Flavin Mononucleotide; Glutathione; Infarction, Middle Cerebral Artery; Male; Mice; Mitochondria; Oxidative Stress; Random Allocation; Reperfusion Injury; Sulfhydryl Compounds

To explore the endogenous and pharmacological activation of neurotrophic mechanisms in a model of brain ischemic lesion in rats.. The study was performed on 170 male albino rats (195-205 g). The model of ischemic stroke was accomplished by the electrocoagulation of the proximal segment of the left middle cerebral artery and simultaneous permanent ligation of the left common carotid artery.. The evaluation of NSE, NO, VEGF, NGF levels in the brain cytoplasmic lysate and plasma showed the delayed activation of neurotrophic mechanisms in astrocytes accompanied by a decrease in delayed alteration of neurons. The use of cytoflavin in the treatment of stroke was accompanied by the earlier and more intense activation of neurotrophic mechanisms in astrocytes, delayed activation of neurotrophic mechanisms in endothelial cells, which promoted neuroprotection in acute ischemic stroke.. Цель исследования - изучение особенностей эндогенной и фармакологической активации нейротрофических механизмов при моделировании острого ишемического повреждения головного мозга у крыс. Материал и методы. Исследование было выполнено на 170 самцах-альбиносах серых крыс. Ишемический мозговой инсульт моделировали путем электрокоагуляции проксимального сегмента левой средней мозговой артерии с одновременным наложением постоянной лигатуры на левую общую сонную артерию. Результаты и заключение. Оценка содержания NSE, NO, VEGF, NGF в цитолизате головного мозга и плазме крови выявила отсроченную активацию нейротрофических механизмов в астроцитах, сопровождающуюся уменьшением отсроченного повреждения нейронов. Применение цитофлавина в лечении инсульта в эксперименте сопровождалось более ранней и более интенсивной активацией нейротрофических механизмов в астроцитах, отсроченной активацией нейротрофических механизмов в эндотелиоцитах, что позволяло на более ранних сроках обеспечить нейропротекцию при развитии ишемического инсульта.

Topics: Animals; Astrocytes; Disease Models, Animal; Drug Combinations; Flavin Mononucleotide; Inosine Diphosphate; Male; Nerve Growth Factors; Neurons; Neuroprotective Agents; Niacinamide; Nitric Oxide; Phosphopyruvate Hydratase; Rats; Stroke; Succinates; Vascular Endothelial Growth Factor A

To compare the effects of cytoflavin and cardioxipin on the emotional status of rats with experimental disturbance of lipid metabolism using the uplifted cruciform labyrinth method.. The disturbance of lipid metabolism was induced by the introduction of exogenic cholesterol-in -oil emulsion in dosage 40 mg /kg of body mass during 20 days. Pharmacological treatment was performed in the 11th day. The drugs were injected intraperitoneally during 10 days: cytoflavin in dose 1,75 ml/ kg (175 mg/kg with succinic acid), cardioxipin in dose 52,5 mg/kg.. Cytoflavin and cardioxipin caused the positive changes in the parameters of emotional status of rats in conditions of experimental dyslipidemia.

Topics: Animals; Anxiety; Disease Models, Animal; Drug Combinations; Dyslipidemias; Emotions; Flavin Mononucleotide; Inosine Diphosphate; Male; Niacinamide; Picolines; Rats; Succinates

The effect of citoflavin and neoton preparations on the migration activity of neutrophil granulocytes under action of mitogen-induced immunocompetent blood cells, Peyer's patches, spleen and inguinal lymph was studied on a group of 55 male chinchilla rabbits with experimental model of widespread purulent peritonitis. It is established that the regulating action of immunocompetent cells on the migration of neutrophil leukocytes under the conditions of widespread purulent peritonitis is stable and widespread process, which is observed within 5 days of the postoperative period. The use of citoflavin and neoton during the postoperative period produces correction of the activity of immunocompetent cells, changing their properties in regulation of the migratory activity of neutrophil granulocytes. The effect is characteristic of both preparations and it is observed in all investigated organs, being manifested to a greater degree in immunocompetent cells of peripheral blood and Peyer's patches. Metabolic preparation citoflavin exhibits a more pronounced immunotropic action in comparison to neoton, which contains creatine phosphate.

Topics: Animals; Cardiotonic Agents; Cell Movement; Disease Models, Animal; Drug Combinations; Escherichia coli; Flavin Mononucleotide; Groin; Humans; Inosine Diphosphate; Lymph Nodes; Lymphocytes; Male; Monocytes; Neuroprotective Agents; Neutrophils; Niacinamide; Peritonitis; Peyer's Patches; Phosphocreatine; Postoperative Period; Rabbits; Spleen; Succinates; Suppuration

One of the most powerful damaging factors during inflammation is hyperactivation of the free-radical oxidation processes. The condition of lipid peroxidation (LPO) and antioxidant activity (AOA) systems in liver has been studied in experiment on 55 male Chinchilla rabbits with widespread purulent peritonitis (WPP) model. The development of WPP leads to expressed of free-radical oxidation processes in liver that is manifested by systemic accumulation of toxic LPO products and a decrease in the activity of antioxidants. Comparative study of the influence of metabolic drugs citoflavin and neoton on the LPO and AOA systems has been conducted. It is established that citoflavin (containing succinic acid) exhibits more pronounced antioxidant properties, provides effective and fast restoration of the balance of LPO and AOA processes, and increases the speed of elimination of free radical.

Topics: Animals; Antioxidants; Cardiotonic Agents; Disease Models, Animal; Drug Combinations; Flavin Mononucleotide; Free Radicals; Inosine Diphosphate; Lipid Peroxidation; Liver; Male; Niacinamide; Peritonitis; Phosphocreatine; Rabbits; Succinates

The aims of our experiments on animals were (i) to evaluate by direct oximery the efficiency of various antioxidant drugs in a complex treatment of acute pancreatitis and (ii) to determine the diagnostic value of the direct oximetry method for estimation of the efficiency of medical treatment. The article presents data obtained in a group 75 outbred Guinea with a model acute pancreatitis, which were treated with mexibel (group 1), emoxipin (group 2), end cytoflavin (group 3), with subsequent investigation of the pancreatic tissues by the direct oximetry method. The obtained results confirmed that the intraperitoneal injection of cytoflavin to animals stimulates tissue respiration, improves metabolism, promotes pancreas recovery, and also improves the prognosis and reduces the lethal outcome. The efficiency of cytoflavin within the complex therapy exceeds the effect of other antioxidants (mexibel and emoxipin) under otherwise equal conditions.

Topics: Acute Disease; Animals; Antioxidants; Disease Models, Animal; Drug Combinations; Flavin Mononucleotide; Guinea Pigs; Injections, Intraperitoneal; Inosine Diphosphate; Niacinamide; Oxygen; Oxygen Consumption; Pancreas; Pancreatitis; Partial Pressure; Picolines; Succinates; Treatment Outcome

An analysis of experimental investigations carried out in 32 dogs and 30 rabbits and laboratory data of 242 patients has shown that the application of antioxidant and antihypoxic medicines decrease reperfusion lesions and endotoxicosis in operative treatment of acute intestinal obstruction.

Topics: Acute Disease; Animals; Digestive System Surgical Procedures; Disease Models, Animal; Dogs; Drug Combinations; Flavin Mononucleotide; Humans; Infusions, Intravenous; Inosine Diphosphate; Intestinal Obstruction; Intestine, Small; Male; Middle Aged; Niacinamide; Rabbits; Reperfusion Injury; Succinates; Treatment Outcome