Influence of Rectal Ozone Application on the Intensity of Free Radical Destruction of Lipids and Intestinal Proteins in the Dynamics of Experimental Colitis.

We studied clinical status, content of products of LPO, and oxidative modification of proteins (OMP) in the lesion focus of the intestine in experimental colitis under conditions of rectal administration of ozone. Experimental colitis was simulated by two-stage administration of oxazolone; rectal insufflation of ozone in the ozone-oxygen mixture was performed daily. The disease activity index (DAI), the content of calprotectin in the feces, and LPO and OMP products in the intestinal homogenate were assessed. On days 2, 4, and 6 of the pathological process, DAI, concentration of calprotectin in feces, content of primary, secondary, and end-products of LPO in the heptane and isopropanol phases, and content of primary and secondary OMP products progressively increases. Under conditions of ozone application, DAI, concentration of calprotectin in feces, the levels of heptane- and isopropanol-soluble primary, secondary, and end-products of LPO, and the level of primary and secondary products of OMP decreased on days 4 and 6; the level of isopropanol-soluble primary, secondary, end-products of LPO increased on day 2 of experimental colitis. The severity of clinical manifestations weakens as the content of LPO and OMP products in the colon decreases on days 4 and 6 of observation.

Effect of Vitamin D3 in Composition of Original Rectal Suppositories on Parameter of Protein Oxidative Modification in Large Intestine in Experimental Ulcerative Colitis.

The effect of vitamin D3 in the composition of original rectal suppositories on the content of products of oxidative modification of proteins in mucous membrane of the large intestine was studied in rats with experimental ulcerative colitis provoked by a two-stage administration of 3% oxazolone. The rectal suppositories with vitamin D3 (1500 IU) were administered every 12 h during 5 days. Condition of the rats was assessed according to disease activity index (DAI), while the content of oxidative modification products of proteins in the homogenate of the mucous membrane was assayed with extraction-spectrophotometric method in the lesion focus of large intestine. DAI increased during entire observation period of ulcerative colitis, which correlated with the level of products of spontaneous and induced oxidative modification of proteins in mucous membrane of the colon. The study examined the pharmaceutical and technological features of novel rectal suppositories of original composition weighing 300 mg, which are based on polyethylene glycol supplemented with aqueous solution of vitamin D3 (10%). The use of rectal suppositories with vitamin D3 reduced DAI and inhibited the oxidative modification of proteins.

Antioxidant Effects of Turmeric Extract in Rectal Suppositories of Original Composition in Experimental Crohn's Disease.

We studied the effect of turmeric extract in the composition of rectal suppositories on the level of LPO products and oxidative modification of proteins in the colon mucosa of Wistar rats with experimental Crohn's disease modeled by rectal administration of trinitrobenzenesulfonic acid. The suppositories containing turmeric extract were administered 12 h after disease induction. On days 3, 5, and 7 of the experiment, clinical parameters of the disease were scored using disease activity scale (DAI) and the concentration of LPO products and intensity of oxidative modification of proteins were measured by the extraction-spectrofluorimetric method. Administration turmeric extract in rectal suppositories reduced the severity of clinical symptoms, the level of LPO products (mostly in the isopropanol phase of the lipid extract), and the total content of products of oxidative modification of proteins. Moreover, correlations between DAI and concentration of LPO products in the colon were found.

Relationship between the change of ethological status and concentration of certain cytokines in blood in experimental desynchronosis under led lighting.

Changing the natural rhythm of day and night leads to the development of DS, disruption of coordinated muscular activity, adequate behavioral activity, a decrease of attention in the performance of night work by experts in various fields. Changes ethological status may potentiate or weaken the changes in the indices of immune status, contribute to the formation of allostatic load at desynchronosis. The purpose: To investigate the relationship between changes ethological status and concentration of certain cytokines in peripheral blood in experimental desynchronosis under LED lighting. Methods: The study was performed on 158 adult guinea pigs, which were randomly assigned into 2 groups: 1 group- animals in the conditions of standard fixed (12 h light / 12 h dark) LED lighting (SFSDO); 2 group- animals with jet lag in terms of LED lighting (DESSDO). Light desynchronosis created by keeping animals at clock coverage for 30 days. Behavioral activity was studied in the test «open field¼ cognitive function was assessed using aqueous «labyrinth¼ Morris. By ELISA was determined on the apparatus in the peripheral blood concentration of interleukin - 4 (IL-4), interferon-gamma (IFN-g), melatonin, cortisol via specific for guinea pig test systems. Results: It was found that in animals of DS in terms of LED lighting in the dynamics of 10-30 days of observation show signs of anxiety, depression orienting-exploratory behavior, reduce the long-term memory and learning ability, spatial orientation disorders. It found that when a jet lag LED lighting conditions for 10 days, 20 days and 30 days in peripheral blood melatonin concentration decreases, the concentration of cortisol rises. In peripheral blood decreased IL-4 concentrations of 20 and 30 days, reducing the concentration of IFN-g at 30 days. Based on the results of correlation analysis, ethological change status and progress of cognitive function with a decrease in the blood concentration of IL-4 and IFN-g, the concentration of melatonin increase cortisol levels. Conclusion: The results indicate that in experimental conditions in desynchronosis LED lighting changes ethological status are associated with the progression of immune status changes.

Antioxidant Effect of Erythropoietin during Experimental Chronic Renal Failure.

The effects of erythropoietin (Epokrin, 900 U/kg) on the parameters of free radical oxidation in the plasma and lymphocytes of peripheral blood were studied in rats with chronic renal failure. We observed accumulation of primary (diene conjugates) and secondary (ketodienes, and conjugated trienes) LPO products in the heptane and isopropanol fractions of blood plasma and a decrease in superoxide dismutase and catalase activities in blood plasma. In lymphocytes, the concentration of primary, secondary and end-products (Schiff bases) of LPO increased in the isopropanol fraction of lipid extract. Treatment with erythropoietin was followed by a decrease in the level of primary and end-products of LPO in the isopropanol fraction of lipid extract of the plasma and lymphocytes and an increase in of superoxide dismutase and catalase activities in the plasma. The content of primary LPO products in the isopropanol fraction of the plasma progressively decreased with increasing superoxide dismutase and catalase activities in the plasma.

Effect of Erythropoietin on Lymphocytes Apoptosis in Experimental Chronic Renal Failure.

Recombinant human erythropoietin was injected intraperitoneally in a total dose of 900 U/kg to rats with experimental chronic renal failure. Suspension of lymphocytes from animals with chronic renal failure was used in vitro, erythropoietin was used in concentrations of 30, 15, 7.5, 3.75, and 1.88 U/liter. Intact cells (Annexin-5-FITC(-)/7-AAD(-)), cells with early signs of apoptosis (Annexin-5-FITC(+)/7-AAD(-)), cells with late signs of apoptosis and partially necrotic cells (Annexin-5-FITC(+)/7-AAD(+)), as well as cells with early signs of necrosis (Annexin-5-FITC(-)/7-AAD(+)) were differentiated by fl ow cytometry. It was found that the number of peripheral blood lymphocytes with early and late signs of apoptosis and necrosis increased in chronic renal failure. Erythropoietin at a total dose of 900 U/kg reduced the number of blood lymphocytes with signs of apoptosis and necrosis and thus elevated the number of intact lymphocytes. Erythropoietin in concentrations ranging from 1.88 to 30.0 U/liter dose dependently lowered the number of lymphocytes with early signs of apoptosis and the number of lymphocytes with the signs of late apoptosis and necrosis in vitro.

Effect of local application of epidermal growth factor on innate immunity and cell composition of destruction focus in experimental thermal injury.

The effect of recombinant human epidermal growth factor (rhEGF) on innate immunity and cellular composition of the destruction focus in the third-degree (IIIA) burn (skin contact with an object heated to 100°C; 4% body surface) was studied in experiments on outbred albino rats. On days 7-28 after burn, blood count of phagocytes and their absorbing capacity and oxygen-dependent metabolism increased, which correlated with the increase in serum IL-1ß level and neutrophil count in the destruction focus. Local application of rhEGF led to earlier (on day 14) normalization of the count and functional activity of blood phagocytes and decrease in serum IL-1ß level and accelerated neutrophil and lymphocyte replacement with fibroblasts in the focus of injury.

Effect of erythropoietin on free radical oxidation and glycoprotein expression in platelets under conditions of chronic renal failure.

A short-term open prospective study examined 62 patients at the terminal stage of chronic renal failure. The experimental group received erythropoietin in a total dose of about 40,000 U. The expression of glycoproteins IIb-IIIa, IIb, and Ib was enhanced, the content of LPO products was elevated, and SOD and catalase activities were reduced in platelets from patients with chronic renal failure. Administration of erythropoietin partially restored free radical oxidation and expression of glycoproteins IIb-IIIa, IIb, and Ib in platelets. A significant correlation was revealed between the expression of platelet receptors on the one hand, and content of LPO products and SOD and catalase activities, on the other hand.

Effects of preliminary hypokinetic stress on sensitivity of the bone marrow to the hypoplastic effect of exogenous glucocorticoid.

We studied the cell composition and free radical oxidation in the bone marrow of white outbred rats after hypokinetic stress (24 and 72 h) and the effects of exogenous glucocorticoid triamcinolone acetonide (2 mg/kg; injected 24 h after hypokinesia); the measurements were performed in 96 h after drug administration. The hypoplastic effect of the glucocorticoid after 24-h hypokinesia was observed against the background of reduced free radical oxidation. In animals subjected to 3-day hypokinesia, the resistance of the bone marrow to the hypoplastic effect of this drug was accompanied by activation of free radical processes.

Effect of erythropoietin on activity of plasma proteolytic systems during experimental renal failure.

Activity of plasma proteolytic systems (fibrin formation, fibrinolysis, and anticoagulant system) and the possibility for correction of changes in these systems with erythropoietin were studied in experiments on outbred albino rats with experimental renal failure. Renal failure was induced by a single subcutaneous injection of mercury chloride (II). The parameters were estimated on day 5 postinjection. Erythropoietin in a single dose of 5000 U/kg was administered on day 4. Renal failure was accompanied by activation of fibrin formation (with factors of the common and intrinsic pathways of blood coagulation), increase in antithrombin activity, and inhibition of the fibrinolytic system. Treatment with erythropoietin led to partial recovery of fibrin formation and fibrinolysis. Under analytical in vitro conditions, 30-min incubation of whole blood from healthy donors with erythropoietin in doses of 1.9-30.0 U/liter was followed by a dose-dependent inhibition of the fibrin formation system and activation of fibrinolysis.

Role of orosomucoid in the regulation of plasma proteolytic systems during experimental renal failure.

Activity of plasma proteolytic systems was studied in outbred albino rats with acute renal failure. The possibility of treating this disorder with acute phase protein alpha-1-acid glycoprotein was evaluated. Acute renal failure was induced by single subcutaneous injection of mercury chloride (II). The parameters were evaluated on day 5 postinjection. alpha-1-Acid glycoprotein in a dose of 150 mg/kg was administered 3 times. Acute renal failure was accompanied by activation of the complement system and fibrin formation (with factors for the intrinsic and common pathways of blood coagulation) and inhibition of the fibrinolytic system and antithrombin activity. Treatment with glycoprotein was followed by partial recovery of fibrin formation and complement system. These changes were probably related to accumulation of glycoprotein in the renal tissue and in situ protective effect.

[Influence of alpha-1-acid glycoprotein on blood rheology].

Hemorheologic effects of alpha-1-acid glycoprotein (AGP) were studied in experiment on 76 noninbred white male rats. AGP was administered i.p. to intact rats twice in a total dose of 300 mg/kg. The effects were evaluated 72 hours after the first injection. It was found that AGP accelerated platelet and erythrocyte aggregation, platelet-erythrocyte cooperation, enhanced adhesion of erythrocytes and agranulocytes to endothelium. On the contrary, adhesion of granulocytes and platelets to endothelium was diminished. Acceleration of platelet aggregation was mediated by stimulation of free radical processes in the cells. Thus, AGP produces anticoagulation action on blood theology.

Effects of alpha1-acid glycoprotein on hemostasis in experimental septic peritonitis.

Pathogenesis of hemostasis disorders in septic peritonitis and the possibility of their correction with acute phase protein (alpha1-acid glycoprotein; two doses of 150 mg/kg) were experimentally studied on outbred albino rats. Platelets count in the peripheral blood and their adhesion to endothelium did not change during peritonitis, while aggregation activity increased due to increased rate and shorter time of aggregation, which was associated with the development of hypercoagulation involving the intrinsic and common coagulation pathways and reduction of antithrombin activity. alpha1-Acid glycoprotein increased platelet count above the normal level, normalized aggregation rate, some blood clotting parameters, and antithrombin activity. Hence, alpha1-acid glycoprotein is a polyfunctional protein modulating all pathogenetic components in the development of blood clotting disorders during septic peritonitis.

Effects of alpha1-acid glycoprotein on free radical oxidation processes in experimental liver failure.

The effects of alpha1-acid glycoprotein (2 intraperitoneal injections in a total dose of 300 mg/kg) on free radical oxidation during liver failure were studied in 53 outbred rats. On day 3 of liver failure, glycoprotein reduced plasma concentrations of free radical oxidation products, elevated the antioxidant potential of the plasma and liver and kidney homogenates, and restored functional reserve and capacity of leukocytes to generation of oxygen radicals.

Ceruloplasmin prevents hemostatic disorders during experimental hyperammonemia.

Experimental hyperammonemia in rats was accompanied by hemostatic disorders manifesting in coagulopathy (activation of the intrinsic pathway of blood coagulation) and suppression of platelet function. Ceruloplasmin in a total dose of 60 mg/kg effectively normalized coagulation hemostasis and functional activity of platelets by improving secretory processes in platelets and increasing aggregation rate.