Mechanism of Stimulation of Myogenesis under the Action of Succinic Acid through the Succinate Receptor SUCNR1.

Effect of succinic acid on the processes of myogenesis was investigated in the study with the cells of C2C12 line. In the concentration range 10-1000 µM, succinic acid stimulated the process of myogenic differentiation, increasing the levels of myogenesis factors MyoD (at all stages of myogenesis) and myogenin (at the stage of terminal differentiation). Presence of the succinate receptors SUCNR1 was revealed in the C2C12 cells using Western blotting, level of which decreased during myogenesis.

The Effect of Original Russian Neurotropic Drugs on Organic Anion Transporting Polypeptides OATP1B1 and OATP1B3.

In experiments on HepG2 cells, we studied the effect of the original domestic neurotropic drugs omberacetam, fabomotizole, and ethylmethylhydroxypyridine succinate (EMHPS) (1-500 μM) on the activity and content of organic anion transporting polypeptides OATP1B1 and OATP1B3. It was shown that omberacetam (500 μM) increased the content of OATP1B1 and OATP1B3, fabomotizole did not affect the level of both transporters, and EMHPS (500 μM) increased the content of OATP1B1 compared to the control and did not affect the level of OATP1B3. The tested substances also reduced the OATP1B1/OATP1B3 ratio, as evidenced by a decrease in the penetration of atorvastatin, a substrate of the transporters, into HepG2 cells in the presence of omberacetam (100-500 μM), fabomotizole (500 μM), and EMHPS (10-500 μM).

Ethylmethylhydroxypyridine Succinate Is an Inhibitor but Not a Substrate of ABCB1 and SLCO1B1.

2-Ethyl-6-methyl-3-hydroxypyridine succinate (EMHPS, Mexidol) is an original antioxidant and an anti-ischemic drug with the possibility of wide applications in the complex therapy of diseases, accompanied by the development of oxidative stress and ischemia; for example, ischemic stroke, chronic cerebral ischemia, and chronic heart failure. The use of EMHPS in the complex therapy of the above diseases may cause the development of drug-drug interactions, particularly pharmacokinetic interactions at the level of transporter proteins. In the present study, we evaluated the interaction of EMHPS with ABCB1 and SLCO1B1.

Generation of a Cell Line Selectively Producing Functionally Active OATP1B1 Transporter.

The solute carrier organic anion transporter family member, OATP1B1, is one of the most important transporter proteins, which mediate penetration of many endogenous substances and xenobiotics into hepatocytes. A model system providing expression of the functional protein is needed to assess interaction of OATP1B1 with various substances. Based on the HEK293 cells, we obtained the HEK293-OATP1B1 cell line, constitutively expressing the SLCO1B1 gene encoding the OATP1B1 transporter.

Pharmacokinetics of Succinate in Rats after Intravenous Administration of Mexidol.

The pharmacokinetics of succinate was studied in Wistar rats after a single intravenous administration of Mexidol in a dose 100 mg/kg body weight. The concentration of succinate in blood plasma, cytoplasmic and mitochondrial fractions of cells of the cerebral cortex, left-ventricular myocardium, and liver was measured by HPLC-MS/MS. After single intravenous administration of Mexidol, succinate was evenly distributed in organs and tissues and quickly eliminated from the body.

Therapeutic Drug Monitoring in Arterial Hypertension.

(1) Background: This study was planned to assess the concentration of antihypertensive drugs (AHD) in the blood serum in patients with controlled and uncontrolled arterial hypertension (AH). (2) Methods: We assessed 46 patients with AH. Based on the results of 24 h blood pressure monitoring (ABPM), the patients were randomized into two groups.

Functioning of P-Glycoprotein during Pregnancy in Rabbits.

The level P-glycoprotein (Pgp) in organs of pregnant rabbits and its content and activity in the placental barrier at different stages of pregnancy were studied. An increase in Pgp content in the jejunum on days 7, 14, 21, and 28 of pregnancy in comparison with this parameter non-pregnant females was revealed by ELISA; in the liver, Pgp content was higher on day 7 and tended to increase on day 14; in the kidney and cerebral cortex, Pgp content was higher on day 28 of pregnancy in parallel with an increase in serum progesterone concentration. We also observed a decrease in Pgp content in the placenta on days 21 and 28 of pregnancy in comparison with day 14 and a decrease in Pgp activity in the placental barrier, which was confirmed by enhanced penetration of fexofenadine (Pgp substrate) through the barrier.

Assessment of Malondialdehyde Belonging to Modulators and Substrates of the P-Glycoprotein Transporter Protein.

In the study on cells of the Caco-2 line, the affiliation of malondialdehyde (MDA) to modulators and substrates of P-glycoprotein (Pgp) was assessed, and the biological role of Pgp in conditions of oxidative stress (OS) was studied. MDA was used at concentrations of 10, 50, 100, and 150 μM; OS was simulated by incubation with hydrogen peroxide (HO) at concentrations of 0.1-100 μM for 24 h.

Mechanisms of P-Glycoprotein Regulation Under Exogenous and Endogenous Oxidative Stress In Vitro.

We investigated the mechanisms of P-glycoprotein (P-gp) transporter regulation in Caco-2 cells under exogenous and endogenous oxidative stress (OS). Exogenous OS was modeled by exposure of the growth medium to hydrogen peroxide at concentrations of 0.1, 0.

Development and validation of a methodology for quantitative determination of malondialdehyde by HPLC-MC/MS.

A bioanalytical technique for quantitative determination of MDA by HPLC-MS/MS. The proposed method for determining MDA includes the release stage of bound MDA and excludes the derivatization reaction. The lower limit of quantitative detection was 600 nmol/l, the volume of the required sample was 10 µl, the analysis time was 7 min.

Regulation and Role of Hypoxia-Induced Factor 1α (HIF-1α) under Conditions of Endogenous Oxidative Stress In Vitro.

The effect of endogenous oxidative stress induced by γ-glutamyl cysteinesynthetase inhibitor D,L-buthionine sulfoximine (BSO) on the functioning of hypoxia-induced factor 1α (HIF-1α) was studied on Caco-2 cells. BSO was added for 24 h in concentrations of 5, 10, 50, 100, and 500 μM. It was shown that BSO in concentrations of 10, 50, and 100 μM induced endogenous oxidative stress and increased the content of HIF-1α; this effect was regulated through nuclear factor of erythroid origin 2 (Nrf2).

[An effect of mexidol on the expression of the transcription factor Nrf2 in the rat cerebral cortex in ischemia].

Aim: To study an effect of the antioxidant and antihypoxant mexidol (ethylmethylhydroxypyridine succinate) on the transcription factor Nrf2 expression in neuronal nucleis of frontal cortex cells autor the common carotid artery unilateral occlusion.

Material And Methods: The study was performed on 64 male Wistar rats. The Nrf2 expression was determined immunohistochemically.

[Mexidol effect on the factor induced by hypoxia HIF-1α expression in the rat cerebral cortex in ischemia].

Unlabelled: The aim of the research - to study the Mexidol (ethylmethylhydroxypyridine succinate) effect on the factor induced by hypoxia (HIF-1α) expression in the frontal cortex of the brain in its ischemia.

Material And Methods: The work was performed on the 64 male Wistar rats. The expression of HIF-1α was determined immunohistochemically.

[Anterior sacral meningomyelocele].

Anterior sacral meningomyelocele is the rarest and least known form of congenital myelocele. It is not manifested externally, it is usually not attended with changes in the neurologic status, and may be regarded as a presacral dermoid cyst. The authors observed 5 members of one family with similar clinical and X-ray signs of such herniations, in 2 they were verified.