MORPHOLOGICAL CHANGES IN MICE LIVER IN DYNAMICS OF CONCANAVALIN A - INDUCED HEPATITIS.

The injure of the liver tissue and its infiltration by cells of the innate and adaptive immunity in dynamics of Con A-induced hepatitis in mice was studied. The semiquantitative method of damage rate of microcirculation channel and liver parenchyma was used, leukocyte liver infiltration and cellular composition of infiltrates were investigated also. Primary liver reaction to the Con-A was the inflammatory changes in the vascular bed, followed by disturbances in the parenchyma.The sufficient increasing of leukocyte migration to the liver was revealed. Besides, the neutrophile infiltration was increased first with a maximum at 6 hours of the experiment (63,9 ±4,6%, p<0,001 to the control level) ,and then the lymphocyte infiltration was increased with creation of manycellular lymphocytemacrophage infiltrates (62% at 48 hours comparing to 6 hours of experiment) and sufficient quantity of plasma cells population (4,9%, p<0,05 comparing to 6 hours of experiment). The obtained data gives the base to suggest that the elevated infiltration of liver tissue by leukocytes, particularly by lymphocytes and monocytes, together with necrotic death increasing creats the conditions for effective intracellular interaction and immune response to autoantigenes. This can be the essential pathogenic mechanism of development of autoimmune liver deseases.

[Genotoxic stress and the pathways of thymus cell death and lymph nodes of mice in conditions of immunocomplex pathology].

There were performed the studies of genotoxic stress and the ways of immunocompetent cells death (apoptosis and necrosis) in the modeling of immune system damage by immunization of CBA mice with the bovine serum albumin. Immunofluorescence studies of immunized mice were established the fixation of immune complexes in liver tissue, spleen, kidney and the aorta. Histological studies of these organs showed vascular system affection and, to a lesser extent, parenchyma. It has been shown that DNA comets index increases in 1,4 time in the lymph node cells and in 1,5 time in the thymus cells in the presence of BSA immunization. We also observed an increase in the number of cells with maximum damage DNA thymus preparations (3.4 fold) and lymph nodes (3.3-fold), respectively, indicating strong genotoxic stress. There were shown the reduce of live ICC number and their death increase, including the pro-inflammatory and immunogenic necrotic way. In that way, data which were obtained on the experimental model is evidenced that generalized immunecomplex pathologic process leads to DNA damage and ICC death both central and peripheral organs of the immune system. ICC genotoxic stress and their death amplification by the necrotic way may play a significant role in the immunecomplex deseases development. These factors of peripheral blood lymphocytes can serve as a prospective test system for assessing the severity of autoimmune and immune complex diseases and their treatment effectiveness.

Effects of NF-κB blocker curcumin on oogenesis and immunocompetent organ cells in immune ovarian injury in mice.

Immunization of CBA mice with extracts from the ovaries of outbred albino mouse led to disorders in meiotic maturation of oocytes, enhanced death of immunocompetent cells in the thymus, spleen, and lymph nodes mainly by necrosis, and promoted the development of inflammatory reaction, as was shown by complete blood count. Treatment with activation inhibitor NF-κB curcumin against the background of immunization significantly reduced disorders in meiotic maturation of oocytes, decreased the number of cells dying by necrosis in immunocompetent organs, and attenuated the inflammatory reaction.

[Effect of inhibitors of cyclooxygenase and lipoxygenase pathways of arachidonic acid oxidation on the immune response and the activity of the monoxygenase system and lipid peroxidation in the spleen and liver in mice]. / Vplyv blokatoriv tsyklooksygenaznogo ta lipoksygenaznogo shliakhiv metabolizmu arakhidonovoï kysloty na imunnu vidpovid', aktyvnist' monooksygenaznoï systemy i perekysnogo okysnennia lipidiv u selezintsi ta pechintsi myshei.

In experiments on CBA mice we studied an immune response (IR) to sheep red blood cells, the activity of monooxygenase system and lipid peroxidation (LP) in a spleen and a liver after administration of indomethacin (IND) and nordihydroguaiaretic acid (NDGA) as the inhibitors of cyclooxygenase and lypoxygenase pathways of oxydation of arachidonic acid consequently. We have found that the both inhibitors changed differently the intensity of IR during its development. IND and NDGA activate the accumulation of antibody-forming cells in the mouse spleen in a dose-dependent fashion at both the inductive and fading phases of IR. At the productive phase these changes are less expressed and they are different depending on the dose of NDGA: the smaller dose increases the immune response and the bigger one decreases it a bit. Changes in the activity of the monooxygenase system in spleen and liver, affected with the both inhibitors, independing on the dose, were of different direction: after IND administration the activity increased, but after NDGA administration it decreased at all the terms of investigation, excluding the term of the 5-th day (productive phase of IR). In these conditions changes in the activity of IR were of opposite direction as compared to the changes in the monooxygenase system.

Effects of carbontetrachloride and chenodeoxycholic acid on hepatic monooxygenase system, lipid peroxidation and some immunologic parameters in rats.

The effect of chenodeoxycholic acid on liver monooxygenase system, lipid peroxidation, lymphocyte proliferation, and immune complexes formation was studied in carbontetrachloride-treated rats. Chenodeoxycholic acid increased the content of both cytochrome P-450 and cytochrome b5 and the rate of aminopyrine N-demethylation in liver microsomal fractions. It also normalized lipid peroxidation in the liver and the proliferative activity of blood lymphocytes activated by phytohemagglutinin. Soon after injection chenodeoxycholic acid caused disturbances of the liver histostructure and of the microcirculation followed by regenerative processes. Liver histostructure tended to return to normal. The level of serum immune complexes was increased. The relationship between the changes in monooxygenase system, lipid peroxidation and immunologic parameters is discussed.

The influence of experimental liver injury on the activity of antigen-induced suppressor cells in murine spleen.

The authors investigated in CBA mice the suppressor cell formation in spleen, induced by injection of a supraoptimal dose of sheep red blood cells and assessed their activity in a passive transfer experiment in animals with liver injury, caused by carbon tetrachloride treatment. The influence of liver explants from mice, treated with carbon tetrachloride, on antigen-induced cells, cultivated together in diffusion chambers, was also studied. It was shown that carbon tetrachloride administration inhibited the antigen-induced suppressor cells formation in murine spleen. Splenocytes, containing antigen-induced suppressor cells from mice treated with carbon tetrachloride, transferred to syngeneic mice together with an immunogeneic dose of sheep red blood cells, caused a smaller decrease of the number of antibody-forming cells in the spleen of recipients than cells from normal mice. The liver explant damaged by carbon tetrachloride, influenced splenocytes, containing antigen-induced suppressor cells (AISC). This influence depended on the degree of liver injury. These data demonstrate the role of liver injury modifying the suppressor activity of splenocytes. The decrease of suppressor cell activity may be one of the mechanisms of enhanced antibody formation in patients with liver diseases.

[The effect of chenophalk on the liver function of intact animals and in experimental hepatitis]. / Vliianie khenofal'ka na sostoianie pecheni u intaktnykh zhivotnykh i pri éksperimental'nom gepatite.

Chenophalk (chenodeoxycholeic acid) was given to Wistar rats, including intact animals and those with chronic toxic hepatitis, in daily oral dose of 15 mg/kg body weight during 11 days. Chronic toxic hepatitis was induced by 7 subcutaneous injections of carbon tetrachloride (0.3 ml of 50% oil solution per kg body weight) each three days. Chenophalk was shown to impair bile crystallization. It enhanced demethylase activity, elevated the levels of cytochromes P-450 and b5 in the liver microsomal fraction, and decreased lipid peroxidation just after injection. The agent normalized oxygen tension in the liver tissue, which had been reduced by carbon tetrachloride. Chenophalk caused disturbances in the structure of the liver and in microcirculation early after injection, showing a tendency to normalize the histostructure of the liver.

[Oxygen-dependent processes in the liver and immunologic reactivity of rats in chronic liver damage induced by carbon tetrachloride]. / Kislorodzavisimye protsessy v pecheni i immunologicheskaia reaktivnost organizma krys pri khronicheskom porazhenii pecheni chetyrkhkhloristymuglerodom.

The chronic hepatitis in Wistar rats was induced by seven subcutaneous injections of carbon tetrachloride (0.3 ml of 50% oil solution per 1 kg of body mass) made each third day. It was shown that cytochromes P-450 and b5 content, demethylase activity in the liver microsomal fraction as well as the oxygen tension in the liver tissue were decreased, while lipid peroxidation was intensified. The PHA-induced blood lymphocyte blastogenesis was inhibited and concentration of circulating immune complexes in the blood was higher than that in intact animals.

[Changes in the activities of antigen-nonspecific helper and suppressor cells in rabbits after carbon tetrachloride-induced liver damage]. / Izmenenie aktivnosti antigennespetsificheskikh T-khelperov i T-supressorov u krolikov v usloviiakh porazheniia pecheni chetyrekhkhloristym uglerodom.

The peripheral blood helper and suppressor T cell activity in rabbits was studied by the method of concanavalin A-induced mitogenesis. Blood lymphocytes were stimulated in vitro with different concentrations of concanavalin A (8 micrograms/ml and 60 micrograms/ml, respectively). The effect of stimulated lymphocytes on proliferative response of allogenic lymphocytes to phytohaemagglutinin was investigated. The liver injury was induced by three-fold subcutaneous injections of carbon tetrachloride (1 ml of 50% oil solution per 1 kg of body mass) each third day. Histological analysis of the liver and T cell activity examinations was performed 2, 9, 16, 30 days after carbon tetrachloride administration. It was shown that the stages of the more pronounced liver injury and the less pronounced regeneration of the liver were accompanied by the increase of helper T cell activity. The stages of the intensive liver regeneration and the less pronounced liver injury were accompanied by the increase of suppressor T cell activity.

[Antigen-specific helper and suppressor activities of T-lymphocytes of the rabbit blood during the development of immunologic response to heterologous erythrocytes]. / Antigenspetsificheskaia khelpernaia i supressornaia aktivnos't T-limfotsitov krovi krolikov v dinamike razvitiia immunnogo otveta na geteroéritrotsity.

A titre of hemolysins in blood serum, helper and suppressor activity of blood T-lymphocytes in response of ++blast transformation to Con A in different doses (8 and 60 ml) and was determined in rabbits after single and two-fold (with an interval of 30 days) immunization of the ram erythrocytes. Examinations were conducted 2, 9, 16 and 30 days after antigen introduction. Peculiarities of changes in antigen-specific helper and suppressor activity of lymphocytes and their balance in dynamics of primary and secondary immune responses are determined.

[Change in the cooperation of T- and B-lymphocytes during the immune response of ram erythrocytes in the presence of liver injury by carbon tetrachloride]. / Izmenenie kooperatsii T- i B-limfotsitov pri immunnom otvete na éritrotsity barana na fone porazheniia pecheni chetyrekhkhloristym uglerodom.

Changes in cooperation of T- and B-lymphocytes induced by the immune response to the ram erythrocytes under conditions of liver injury by CCl4 in donors of cells or recipients have been studied on CBA line mice in the adaptive transfer system. It is stated that application of CCl4 induces changes in functional properties of T- and B-lymphocytes and process of their cooperation. The pattern of these changes is determined by periods passed after application of the hepatotropic poison, e. i. by the degree of the liver injury and by the stage of the pathological process in it. Application of CCl4 exerts more pronounced inhibiting effect on B-lymphocytes than on T-lymphocytes.

[Effect of antihepatocytotoxic serum on processes of cellular and intracellular regeneration of pathologically altered liver]. / Vliianie antigepatotsitotoksicheskoi syvorotki na protsessy kletochnoi i vnutrikletochnoi regeneratsii patologicheski izmenennoi pecheni.

The parameters of the liver regeneration: mitotic index, DNA synthesis, nucleolar size of hepatocytes and histological structure, were studied in adult female rats with CCl4-affected liver during administration of the gamma-globulin fraction of antihepatocytotoxic serum (gamma-AHCS). It was shown that in various periods after exposure to CCl4 either the cellular processes of regeneration are predominant or the intracellular ones. gamma-AHCS (0.06 microgram protein per 100g body weight/one injection) intensifies and makes longer both the processes.