Algorithm of Molecular and Biological Assessment of the Mechanisms of Sensitivity to Drug Toxicity by the Example of Cyclophosphamide.

Comparative study of the liver, blood, and spleen of DBA/2JSto and BALB/cJLacSto mice sensitive and resistant to acute toxicity of the cyclophosphamide allowed us to reveal basic toxicity biomarkers of this antitumor and immunosuppressive agent. Obtained results can be used for the development of an algorithm for evaluation of toxic effects of drugs and food components.

[Role of mineral elements in the immunological effects, activation nuclear transcription factor of NF-kappaB and matrix metalloproteinase].

Today chemical elements draw to themselves the increasing attention the immunological effects performance of a role of activators and inhibitors some many enzymes, active participation in inflammation processes that, undoubtedly, assumes their participation in cellular and humoral immunity. Main objective of the present review was attempt to consider a role and value of chemical elements in maintenance of a microelement homeostasis, interaction with immune system, their value in system proteolysis and regulation of antineoplastic immunity. The special attention of researchers is involved with the questions connected with ability of immune system to perceive and process pathogens with participation nuclear transcription of the factor NF-kappaB.

Flavonoids and resveratrol as regulators of Ah-receptor activity: protection from dioxin toxicity.

In 2002 FAO and WHO published a joint appeal to state and public organizations and scientific community to take every effort to control the contents of dioxin and related biphenyls in the environment and food products. The toxic effects of dioxin are realized via its interaction with the Ah-receptor. Here we reviewed modern notions about the structure and functions of Ah-receptor.

[Synthesis of 1-hydroxyalkyl-3-substituted ureas and thioureas as a substrates for alcohol dehydrogenase].

A series of 1-(2-hydroxyethyl)- and 1-(3-hydroxyethyl)-3-substituted ureas and thioureas were synthesized. 1-(3-Hydroxyethyl)-3-acylthioureas were shown to be specific substrates for alcohol dehydrogenase in vitro.

[Synthesis of uracil and theophylline derivatives and study of their effect on glucose transport in rat hepatic cells].

A series of uracil and theophyllin derivatives were synthesized. 4-Amino-1,3-dimethyl-5-nonanoylaminouracil displayed the most pronounced effect of the in vitro stimulation of the 2-deoxyglucose transport into hepatic rat cells.

[Synthesis and antiproliferative activity of a novel N-acyl derivative of doxorubicin].

Doxorubicin was acylated with estrone 3-hemisuccinate. The modified derivative exhibited high antiproliferative activity in vitro toward cell cultures of the MCF-7 human mammary adenocarcinoma and HepG2 human hepatoma.

[Activity of enzymes of xenobiotics metabolism in peripheral blood lymphocytes in man].

The activity of NADPH-cytochrome c-reductase, benzpyrene hydroxylase, epoxy-hydratase and glutathione-S-transferase in human peripheral blood lymphocytes was studied. In the presence of NADPH, native lymphocytes were unable to reduce cytochrome c. In order to improve the availability of substrates for enzymes, lymphocytes were degraded by single-stage freezing-melting.

[Comparative study of the effectiveness of the classical and modified Cooper protocol for breast cancer chemotherapy].

Efficiency of routine and modified Cuper procedures was studied after evaluation in saliva and urine of women with mammary gland tumor of the following parametres: alterations in dynamics of acrolein excretion with saliva, dynamics of alterations in calculated therapeutic doses of cyclophosphane administered using these procedures, dynamics of the ratio between non-metabolized cyclophosphane and its initial level in urine of the patients. Analysis of the data obtained suggest that the liver tissue enzymatic systems, involving in biotransformation of cyclophosphane, were distinctly less impaired during the modified Cuper procedure as compared with the routine course, thus corroborating advantages of the modified procedure used in chemotherapy of patients with mammary gland tumor.

[The effect of finoptin on the metabolism and pharmacological action of cyclophosphane in vivo and in vitro].

Phynoptin (Ph) and cyclophosphamide (CP) gave rise to a type I spectral changes with liver microsomal fraction. KS were 15 microM and 2150 microM, respectively. Ph increases the concentration of NBP product(s) of CP and acrolein in the blood plasma of animals.

[The role of secondary metabolism in formation of benz(a)pyrene dihydrodiol profile in microsome membranes].

4,5-, 7,8- and 9,10-dihydrodiols of benz(a)pyrene (BP) were separated by thin-layer chromatography and their influence on BP-hydroxylase activity was studied in liver microsomes isolated from rats treated with phenobarbital (PB-microsomes) and 3-methylcholanthrene (MC-microsomes). All diols studied inhibited hydroxylation of BP by the competitive type. Accumulation of BP-diols in the incubation media correlated with their affinity to cytochrome P-450 isoenzymes which catalyzed the secondary metabolism of these diols.

[The role of vitamin K3 in the hydroxylation of benz(a)pyrene in rat liver mitochondria after induction with 3-methylcholanthrene and phenobarbital].

The "fast" phase reduction of microsomal cytochromes P-450 and P-448 and their benz(a)pyrene (BP) hydroxylase activity was investigated as a function of menadione concentrations. Within a narrow concentration range (1.5-3 microM) menadione activates cytochrome P-448 reduction and the BP hydroxylase activity.

[Influence of the fermentative cross-seams on the structure of the microsomal membrane].

In rat liver microsomes freezing with subsequent thawing led to irreversible redistribution of protein-lipid packing. This redistribution was detected by a change in the efficiency of energy transfer between protein aromatic groups of membrane protein and lipid-soluble fluorescent probe pyrene. Transglutaminase pretreatment of microsomes prevented the irreversible redistribution.

[Reduction of spin labels with ascorbic acid in solution and on biomembranes].

Dependence of the rate of nitroxyl radical reduction with ascorbic acid upon pH, ionic force, temperature, type of radical and dielectric constant of the solvent is reported. The factors mentioned are essential for interpreting the results obtained for biomembranes. It is shown that under physiological pH the reduction is determined by ascorbic acid monoanion and unprotonated radical interaction.

[Study of spin-labeled microsomal membrane proteins by their reaction with ascorbic acid].

Kinetics of the reduction of nitroxyl radicals bound to SH-groups of microsome membrane proteins by ascorbic acid was investigated. The reduction involves two steps. During the first quick step mainly the radicals with weak immobilization located on the membrane surface are reduced.

[Cytochrome P-450 distribution in endoplasmic reticulum membranes of rat liver].

Using electron-dense labelling in combination with solubilization, the localization of cytochrome P-450 in the microsomal membranes was studied. It was shown that cytochrome P-450 is unevenly distributed in the membrane and has 2-3 reactive SH-groups. The molecules of solubilized cytochrome P-450 contain 4-5 reactive SH-groups and show a tendency to aggregate.

[Accessibility of microsomal membrane proteins for protease K].

The effect of protease K on the microsomal membrane proteins was studied. It was shown that treatment of the microsomal membranes by low concentrations of protease did not remove more than 35% of total membrane proteins. Treatment by higher protease concentrations removed about 50% of the proteins.