[Laboratory model of hyperlipidemia].

AIM: Approbation of laboratory model of hyperlipidemia induced by multiple administration of poloxamer 407 to hybrid mice (C57BL/6 x DBA/2) F1. MATERIALS AND METHODS: Two-month-old female mice (C57B1/6 x DBA/2)F1 were used for experiments. Level of dyslipidemia was assessed measuring cholesterol level in serum by method with cholesteroloxidase. RESULTS: Dosages and timing of administration of the compound for inducing stable moderate hypercholesterolemia were selected. It was discovered that dyslipidemia induced by this method accompanied by reliable increase of neutrophils count in peripheral blood of animals. CONCLUSION: Hyperlipidemia induced in mice by administration of poloxamer 407 could be used for convenient experimental model for complex studies of immune system functions during pathophysiologic conditions associated with lipid metabolism disorders.

[Influence of the activation of the immune system cells on the parameters of lipid metabolism in macrophages]. / Vliianie aktivatsii kletok immunnoi sistemy na parametry lipidnogo obmena v makrofagakh.

The influence of tumor necrosis factor a (TNF-alpha) and media, conditioned by activated macrophages and lymphocytes and containing a complex of biologically active compounds (including cytokines), on the parameters of lipid metabolism in macrophages was studied. The addition of recombinant TNF-alpha and immunocompetent cell-conditioned media to mouse peritoneal macrophages culture stimulated labelled oleate incorporation into cholesterol esters and triglycerides, as well as labelled glycerine incorporation into cholesterol esters, but inhibited labelled cholesterol incorporation into cholesterol esters. One of the mechanisms of the influence of activated immunocompetent cells on cholesterol metabolism in macrophages was, supposedly, the stimulation of sphigmomyelinase activity by a complex of anti-inflammatory cytokines produced by these cells on their activation.

[Effect of modified low density lipoproteins on humoral immune response and functional activity of macrophages in mice]. / Vliianie modifitsirovannykh lipoproteinov nizkoi plotnosti na gumoral'nyi immunyi otvet i funktsional'nuiu aktivnost' makrofagov myshi.

Intravenous injection of acetylated low density lipoproteins (acLDL) in mice in a dose of 0.5 mg per mouse decreased the intensity of humoral immune response to sheep red blood cells (SRBC) by 35%. The addition of acLDL to mouse peritoneal macrophages in vitro resulted in inhibition of Fc-dependent phagocytosis of SRBC and fourfold increased secretion of prostaglandins E2 by macrophages. Fc-dependent phagocytosis of SRBC was also found to be inhibited by oxysterols (25-hydroxycholesterol and 7-ketocholesterol), added to the incubation medium of macrophages in vitro in doses of 0.5-5 mg/ml. The conclusion was made that oxidative metabolism of cholesterol and arachidonic acid, contained in LDL, may mediate the immunomodulating effects of modified LDL.

[Effect of cytochrome P-450 inhibitors on oxidative modification of low-density lipoproproteins by macrophages]. / Vliianie ingibitorov tsitokhroma P-450 na okislitel'nuiu modifikatsiiu lipoproteinov nizkoi plotnosti makrofagami.

Unlike other cytochrome P450-dependent oxygenase inhibitors, ketoconazole has been shown to suppress the murine macrophage-mediated oxidative modification of human low-density lipoproteins (LDL) in a dose-dependent manner. The benzo[alpha]pyrene-induced microsomal monooxygenase activity was accomplished by a 1,5-fold increase in LDL oxidation by macrophages, ketokonazole (20 mu), methoxalene (20 mu), and alpha-naphthaflavone (50 mu). Ketoconazole was also effective in inhibiting macrophageal NADPH oxidase and LDL autooxidation induced by Fe2+ rather than Cu+, which is likely to be associated with its ability to act as a chelator of free and heme-bound iron ions.

[Cytochrome P-450-dependent monooxygenase activity and the functions of immunologically competent cells]. / Aktivnost' tsitokhrom P-450-zavisimykh monooksigenaz i funktsii immunokompetentnykh kletok.

The authors summarize the data on the interrelationship between cytochrome P450-dependent monooxygenase system activity in immunocompetent cells and their functional properties, provide the results of experimental research showing an important role this enzyme system plays in macrophages and lymphocytes and the influence of immunoactive substances on their activity. The data amassed support the immunomodulating effects of cytochrome P450 inducing substances. In a majority of cases their action manifests itself in the suppression of different functions of immunocompetent cells. The role of Ah-receptor and other biochemical mechanisms in the development of those effects is discussed. Emphasis is laid on the fact that the high sensitivity of the immune system to the action of xenobiotics and the diversity of their influences on immune responses depend to a large measure on the activity of the enzyme systems metabolizing antibiotics.

[Effect of the monooxygenase activity inhibitor ketoconazole on cholesterol esterification in mouse peritoneal macrophages]. / Vliianie ingibitora monooksigenaznoi aktivnosti ketokonazola na ésterifizkatsiiu kholesterina v peritoneal'nykh makrofagakh myshi.

In order to determine the feasible role of monooxygenases in regulation of the macrophage acyl-CoA: cholesterol acyltransferase (ACAT) activity, the effects of ketoconazole on the activities of benz(a)pyrene hydroxylase and ACAT as well as on the [14C]oleate incorporation into cholesterol esters in cultured mouse peritoneal macrophages (MPM) were studied. Ketoconazole (0.5-50 M) inhibited the benz(a)pyrene hydroxylase activity but increased the free cholesterol (FC) level in MPM cultured with an acetylated low density lipoprotein (acetyl-LDL). An addition of ketoconazole (1-50 M) eliminated the increase in the rate of FC esterification after incubation of MPM with acetyl-LDL (but not with 25-hydroxycholesterol). In contrast, progesterone, an ACAT activity inhibitor, used at 5-30 M diminished the rate of FC esterification, when MPM were incubated with acetyl-LDL of 25-hydroxycholesterol. Ketoconazole provoked a dose-dependent decrease of the [3H]FC incorporation into macrophage polar oxysteroids. The data obtained suggest that the ketoconazole (1-30 M) effect on FC esterification in MPM cultured with acetyl-LDL is determined by its inhibiting monooxygenases, which produce oxidized forms of FC that are potential activators of ACAT.

[Effect of the superoxide radical on lymphocyte proliferation stimulated by a mitogen]. / Vliianie superoksidnogo radikala na proliferatsiiu limfotsitov, stimulirovannuiu mitogenom.

Administration of superoxide dismutase or a complex of divalent copper with lysine to human and mice lymphocyte cultures was shown to prevent from the lymphocyte proliferative response to concanavalin A stimulation. The inhibition grade dependence on the inhibitor concentration in culture medium was studied. It is concluded that active oxygen forms produced by macrophages may be factors defining the value of proliferative response of lymphoid cells under mitogen stimulation.

[Effect of hydrocortisone on superoxide radical production by phagocytosing spleen cells]. / Vliianie gidrokortizona na produktsiiu superoksidnogo radikala fagotsitiruiushchimi kletkami selezenki.

Superoxide radical production by mouse phagocytic spleen cells was shown to be essentially increased 2 hours following intraperitoneal injection of hydrocortisone acetate at a dose of 50 mg/kg body weight. The addition of hydrocortisone to the suspension of mouse spleen cells has resulted in linear dependence of hormone concentration in the incubation medium on the maximum rate of superoxide radical production. The mechanism of hydrocortisone stimulating effect on the activity of plasma membrane-located NAD(P)H-oxidase of phagocytic cells is being discussed.

[Effect of microsomal monooxygenase inductor zixoryn on clinico-immunologic indicators in allergologic patients]. / Vliianie induktora mikrosomal'nykh monooksigenaz ziksorina na kliniko-immunologicheskie pokazateli u allergologicheskikh bol'nykh.

Zixorine, an inducer of microsomal monoxygenases, can effectively be used for the treatment of patients with allergic dermatoses. It has been established that zixorine makes the NBT-test and the IgE content in the blood serum of these patients return to normal.

[Quantitative method of determining the activity of multiple forms of superoxide dismutase]. / Kolichestvennyi metod opredeleniia aktivnosti mnozhestvennykh form superoksiddismutazy.

A quantitative method for determination of the activity of multiple superoxide dismutase (SOD) forms is presented. The method is based on SOD electrophoretic separation on polyacrylamide gels, elution from gels and determination of inhibition of nitro blue tetrazolium reduction in the NADH2 + phenazinemetasulphate system. As shown, partially purified SOD from bovine erythrocytes separated into three fractions. The activity of form 2 proved to be much lower than the degree of its staining for protein.