Vera I. Smolyakova

Aim. To investigate morphological alterations in neurons and glial cells in the cerebral cortex using a rat model of total transient global cerebral ischemia (GCI) and to evaluate the neuroprotective effects of p-tyrosol. Materials and methods. Experiments were performed on Wistar rats ( n = 30), randomly divided into three groups: sham-operated, GCI control, and GCI with p-tyrosol treatment. The glioneuronal elements of the cerebral cortex were analyzed by light and transmission electron microscopy combined with a quantitative morphometric assessment. Results. In the GCI group, a significant reduction in neuron density was observed. Surviving neurons showed a marked decrease in the relative volume of membrane-bound organelles, accompanied by an increase in lipofuscin, lysosomes, and vacuoles. Administration of p-tyrosol after GCI enhanced neuronal survival. Conclusion. For the first time in this rat model of GCI, structural and ultrastructural changes of cortical neurons and glial cells in rats were characterized, confirming the validity of the model. Neuroprotective effects of p -tyrosol in the context of GCI were demonstrated at both the light-microscopic and ultrastructural levels.

Introduction: The inflammatory response to cerebral ischemia plays a crucial role in stroke outcome. This study focuses on the neuroprotective effects of tryptanthrin, a plant alkaloid with anti-inflammatory activity, in the rat model of focal cerebral ischemia (FCI). Materials and Methods: The neurological status of animals was assessed at 4, 24, and 48 hours after FCI (1-hour occlusion of the left middle cerebral artery) in male Wistar rats; the infarct size was assessed 48 hours after reperfusion. Rats received intraperitoneal injections of 6 and 12 mg/kg tryptanthrin or vehicle (control group) 30 min and 23 and 47 hours after FCI. The effects of 12 mg/kg tryptanthrin on the IL-1β and TNFα levels in brain tissue, blood brain barrier (BBB) permeability, and cerebral edema were assessed 24 hours after FCI. Results: Tryptanthrin administration at a dose of 12 mg/kg significantly reduced the neurological deficit and infarct size compared with the corresponding values in control rats. Tryptanthrin administration at a dose of 6 mg/kg was ineffective. The IL-1β and TNF-α levels in cerebral infarction focus, the Evans blue content in the left (affected) hemisphere, and water content in the supra- and subventricular structures of the affected hemisphere increased 24 hours after FCI. Tryptanthrin administration (12 mg/kg) significantly attenuated the TNF-α level in the cerebral infarction site. The values of BBB permeability and water content in the experimental group did not significantly differ from the corresponding values in sham-operated rats. Conclusion: Obtained data suggested that tryptanthrin may be considered an agent with significant neuroprotective properties, which provides rationale for further studies of this compound as a potential neuroprotector with anti-inflammatory mechanism of action.

The liver is a vital multifunctional organ that plays a central role in numerous metabolic processes, including the regulation of blood glucose levels, as well as the synthesis, storage and redistr...

IBP (2,6-diisobornyl-4-methylphenol) is a camphene derivative with unique pharmacological properties and low toxicity. It exhibits pronounced antioxidant and membrane-protective effects, making it a promising cardio- and neuroprotector.The aim of the study was investigating the pharmacokinetics of IBP in rats after intravenous (1 mg/kg) and oral administration at three doses (10, 25, 50 mg/kg). Specifically, we focused on assessing the bioavailability and dose proportionality following oral administration.Blood samples were collected via a jugular vein catheter, and plasma samples were analyzed using a validated HPLC-MS/MS method. The calculation of pharmacokinetic parameters was performed by both non-compartmental and compartmental approaches. The proposed dosage form for intravenous administration was a multicomponent mixture containing N-methyl-2-pyrrolidone.Concentration of IBP in the body after intravenous administration decreased over time, exhibiting bi-exponential decay kinetics. IBP reached peak concentrations immediately and was rapidly distributed into the peripheral compartment after intravenous administration. The systemic exposure after oral administration was proportional to the dose. The calculated absolute oral bioavailability of IBP was no more than 20%.The value of the average half-life of IBP after intravenous administration exceeded similar values after oral administration by 1.5-1.6 times.

1.The dose proportionality and bioavailability of the potential anti-inflammatory and neuroprotec-tive JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime (IQ-1) were evaluated by comparing pharmacokinetic parameters after single oral (25, 50 and 100mg/kg) and intravenous (1mg/kg) IQ-1 administration in rats.2. IQ-1 and its major metabolite ketone 11H-indeno[1,2-b]quinoxalin-11-one (IQ-18) were isolated from plasma samples by liquid-liquid extraction. IQ-1 (E-isomer) and IQ-18 were simultaneously quantified in plasma by the validated method of liquid chromatography with triple quadrupole mass spectrometry (HPLC-MS/MS).3. The absolute bioavailability of IQ-1 was <1.5%. Cmax values were 24.72 +/- 4.30, 25.66 +/- 7.11 and 37.61 +/- 3.53ng/mL after single oral administration of IQ-1 at doses of 25, 50 and 100mg/kg, respectively. IQ-1 exhibited dose proportionality at 50-100mg/kg dose levels, whereas its pharma-cokinetics was not dose proportional over the range of 25-50mg/kg. IQ-18 demonstrated the invariance of the dose-normalized Cmax.4.In this study we systematically elucidated the absorption characteristics of IQ-1 in rat gastrointes-tinal tract and provided better understanding of IQ-1 pharmacology for the future development of a new formulations and therapeutic optimisation.

Антитромботическая активность производного индолинона – стимулятора растворимой гуанилатциклазы

Защита миокарда диборнолом в условиях множественной ишемии/реперфузии у крыс

Механизмы нейропротективного действия п-тирозола в условиях тотальной транзиторной ишемии-реперфузии головного мозга

We compared bioavailability of 4-methyl-2,6-diisobornylphenol after single intragastric administration to rats in a dose of 200 mg/kg in starch suspension and in almond oil. Absorption of 4-methyl-2,6-diisobornylphenol in the gastrointestinal tract after administration in almond oil was much more efficient than after administration in aqueous starch mucus.