[Effect of NF-kappaB activation inhibitor curcumin on the oogenesis and follicular cell death in immune ovarian failure in mice].

In experiments on CBA mice, we studied the influence of an inhibitor of nuclear transcription factor kappaB activation curcumin, obtained from Curcuma longa, on the meiotic maturation of oocytes and apoptotic and necrotic death of follicular cells at immune ovary failure induced by immunization of animals with allogenic ovarian extracts. NF-kappaB plays a pivotal role in the induction of genes encoding pro-inflammatory factors (cytokines, adhesion molecules, inducible NO-synthase and cyclooxygenase) and in regulation of cell proliferation and death. It has been shown that immunization of mice increased the death of follicular cells through anapoptotic and necrotic pathways, which led to inflammatory response (according to blood leukogram and impairment the oocyte meiotic maturation at metaphase I and II). Intragastric administration of curcumin (Sigma, USA, 2 mg of the mouse weight, four times a week during the period of immunization) reduced the number of the follicular cells died through apoptotic and especially necrotic pathway. Curcumin attenuated an inflammatory response and improved the meiotic maturation of oocytes impaired under experimental immune ovarian failure in mice.

[Proliferation and death of liver mononuclear cells in immune lesions induced by concanavalin A and anti-liver antibodies in mice].

Two types of experimental liver failure in mice were investigated to study the immune mechanisms of liver disease: 1) T-cell-mediated injury induced by administration of concanavalin A (ConA) and 2) antibody-mediated injury induced by administration of anti-liver antibodies (ALA, gamma-globulin fraction of sera from rabbits immunized with liver tissue). It was established, that both types of liver injury were accompanied by the activation of immune processes in the liver, as shown by the increase of liver mononuclear cell proliferation, estimated using IPO-38 monoclonal antibodies. In contrast to ConA treatment, the immune activation under ALA-treatment was also associated with the increase in the percentage of plasma cells and small lymphocytes in liver mononuclear cells. At the same time, an increase in apoptotic and necrotic mononuclear cell death was more pronounced under ConA-treatment. This was accompanied by enhanced Fas receptor expression in these cells. Thus, it was shown that in case of T-cell mediated liver injury, the balance between cell proliferation and cell death in mononuclear liver cells was shifted toward the significant increase of apoptotic and necrotic cell death, particularly Fas-mediated apoptosis, while immune processes activation and cell proliferation were more pronounced in the case of antibodies-mediated injury.

[The protective effect of molsidomin in immune ovarian pathology in mice].

Experimental immune ovarian failure in CBA mice was induced by either administration of xenogenic anti-ovarian antibodies (scheme 1) or immunization with allogenic ovarian extracts (scheme 2). It was shown that both types of treatment impaired the meiotic maturation of oocytes: the number of cells at the stages of metaphase I and metaphase II decreased compared to the cells of control mice. In both schemes of experiments, impaired oogenesis was accompanied by reduction of percentage of viable follicular cells and by increase in the part of cells possessing morphological features of apoptosis. In contrast, the number of necrotic follicular cells increased in scheme 2 only. The donor of nitric oxide molsidomin (10 mg/ kg), when injected an hour before administration of xenogenic anti-ovarian antibodies or allogenic ovary extracts, improved the meiotic maturation of oocytes and favored follicular, lymph nodes and thymus cells survival by decreasing the number of apoptotic and necrotic cells.

[Death of the ovarian follicular cells in mice with impaired oogenesis of the immune nature].

An impairment of the meiotic maturation of the oocytes has been shown in vitro for 2 types of immune damage of the ovaries in mice induced by xenogenic antiovarial antibodies and immunization with allogenic ovaria. Impairment of the oogenesis was followed by the follicular cell death, primarily by on the apoptic way, but under the immunization with allogenic ovary a necrotic way of their death was also activated.

[The role of nitric oxide in the development of humoral immune response in mice].

The immune response in CBA mice was evoked by injection of sheep erythrocytes. The number of antibody-producing cells in the spleen, as well as nitric oxide production, oxygen-dependent metabolism and 5"-nucleotidase activity of peritoneal macrophages and lymphocytes were studied on days 1-5-14 after immunization. It was shown that during the inductive phase of the immune response (day 1), the peritoneal cells increased nitric oxide production, while later their functional activity increased and NO level became normal. The use of NO-synthase inhibitors (non-selective L-NNA and iNOS inhibitors SMT and dexamethasone) increased the immune response and decreased the macrophage functional activity. The use of NO-donator SNP resulted in reverse effect: decrease of the immune response and stimulation of peritoneal cells functional activity. The data obtained indicate that nitric oxide participates in the immune response regulation, in particular, through the suppressive effect of macrophages.

[Effect of inhibitors of cyclooxygenase and lypoxygenase pathway of metabolism of arachidonic acid on the development and suppression of the immune response in mice]. / Vplyv blokatoriv tsyklo- ta lipoksyhenaznoho shliakhiv metabolizmu arakhidonovoï kysloty na rozvytok i supresiiu imunnoï vidpovidi u myshei.

The influence of indomethacin (IM) and nordihydroguaiaretic acid (NDGA) as inhibitors of cyclooxygenase and lypoxygenase pathways of arachidonic acid metabolism, accordingly, on the development of the immune response (IR) to sheep red blood cells (SRBC), as well as on the formation and functional activity of the antigen-induced (by the tolerogenous dose of SRBC) T-suppressors (AITs) was studied. Investigation was carried out on mice of line CBA. The IR was estimated by quantity of antibody-forming cells in the mouse spleen. The functional activity of AITs was determined in the transfer adopting system by the intensity of IR suppression in mice--recipients. The data obtained have demonstrated, that both inhibitors mainly stimulated the IR which was more expressed at NDGA application and depended on a phase of the IR. The stimulation of the IR was related with a suppression of AITs and a decrease in their functional activity.