Correction of Acute Parodontitis with Indolicidin Analogues.

We studied the influence of synthetic indolicidin analogues on the development of acute periodontitis. The corrective effect was found in indolicidin analogues Nos. 7 and 8; it manifested in a decrease in the edema of gingival epithelium and lamina propria, a decrease in the relative area of inflammatory infiltrates, and a significant increase in the relative area of normal connective tissue. These changes were revealed as soon as on day 14 and were most pronounced in 21 days after the removal of the ligature. Indolicidin analogues Nos. 7 and 8 demonstrated similar effectiveness on the model of acute periodontitis.

Effects of Opioid Peptides on Changes in Lipid Metabolism in Rats Subjected to Swimming Stress.

Blood levels of nonesterified fatty acids, total cholesterol, triglycerides, and LDL increased in rats subjected to forced swimming stress. Administration of opioid peptides dynorphin A(1-13), DSLET, or DAGO reduced stress-induced disturbances in lipid metabolism. Dynorphin A(1-13) and DAGO produced the most pronounced effects and prevented an increase in concentrations of nonesterified fatty acids, triglycerides, total cholesterol, and LDL as soon as 39 h after treatment. Only DSLET increased HDL content in the plasma of stressed rats. The observed effects can be explained by the stress-limiting effects of opioids, e.g. attenuation of the effect of catecholamines on the adipose tissue and inhibition of the generation LPO products suppressing activity of the cholesterol metabolizing enzyme.

[THE INFLUENCE OF OPIOID PEPTIDES DSLET AND DAGO ON LIPID PEROXIDATION AND THE ACTIVITY OF ANTIOXIDANT ENZYMES IN THE LIVER TISSUE OF RATS IN THE STRESS OF DIFFERENT DURATION].

It was established that immobilization stress of different duration (3, 6 or 12 hours) causes the activation of lipid peroxidation in liver tissue of rats 39 hours after stressor action. Activation of lipid peroxidation within 7 days was observed in animals exposed to 6 or 12 hours stress. The activation of superoxide dismutase and catalase activity was revealed in rats after 3 hours immobility, but 12 hours stress was accompanied by superoxide dismutase inhibition. Agonists of different opioid receptors were shown to afford the antioxidant effects inhibiting the accumulation of malondialdehyde and acylhydroperoxides in the liver tissue and stimulating the antioxidant enzyme activity. Opioid peptides had a stimulatory effect on superoxide dismutase activity and less one on catalase activity in animal exposed to immobilization of different duration. A selective agonist of opioid delta-receptors DSLET manifested more expressed antioxidant effect, causing the inhibition of LPO metabolites production and the stimulation of superoxide dismutase and catalase activity.

[THE INFLUENCE OF OPIOID PEPTIDES ON LIPID PEROXIDATION AND ANTIOXIDANT ENZYME ACTIVITY IN RATS AFTER SWIMMING STRESS].

It was established in experiments on rats, that injection of opioid peptides DAGO (a selective igonist of opioid mu-receptors), DSLET (a selective agonist of opioid delta-receptors) or dynorpiin A (1-13) (a selective agonist of opioid kappa-receptors) decreased the stress-induced activatin of lipid peroxidation in liver tissue and plasma. A selective agonist of opioid mu-receptors) AGO manifested the most expressed activity. The using of investigating peptides caused the increase of superoxiddismutase activity in liver tissue. The reinforcement of catalase activity was )bserved in DSLET or dynorphin A (1-13). DAGO decreased its activity. The peptide effects of lifferent directions oncatalase activity in plasma were established. These effects can be explained y the stress-limiting action of peptides in entire organism, the peculiarities of opioid receptors spreading in liver tissue and by the influence of preceded load with non-complete oxidized sub stances after intensive swimming on the opioid receptor affinity.

[The influence of dynorphin A (1-13) on lipid peroxidation and antioxidant enzymes activity in the immobilization stress of different duration].

It was revealed in experiments on rats, that selective agonist of opioid kappa-receptors dynorphin A (1-13) has expressed antioxidant action in immobilization stress of different duration. It manifests itself with the decreases of the content of lipid peroxidation metabolites in liver tissue. It was shown, that the effect of this peptide on the activity of antioxidant enzymes superoxiddismutase and catalase depends on the stress duration. The stimulatory influence of peptide on catalase activity was shown in the rats after 3-hours immobilization, but the analogue effect of dynorphin was less in the animals after 6-hours or 12-hours stress. The stimulatory action of dynorphin A (1-13) on the superoxiddismutase activity was established in the rats after 6-hours or 12-hours immobilization within the experiment period, but peptide had no effect in the rats after 3-hours stress.

[The influence of melatonin on the content of lipid peroxidation metabolites and antioxidant enzyme activity in the liver of rats after immobilization].

The modeling of acute immobilization stress caused the increase of the content of lipid peroxidation metabolites and the decrease of the activity of superoxiddismutase and catalase in liver tissue within 4 days after stress. Melatonin in dose 0.2 mg/kg had a weak antioxidant effect and increased superoxiddismutase activity. The injection of melatonin in dose 1.0 mg/kg caused the significant decrease of lipoperoxidation metabolites content in liver tissue 39 hours after stress. On fourth and seventh days of the experiment there were no differences in malonic dyaldehyde content between these animals and naive ones. The concentration of acylhydroperoxides was significantly less than in control and naive groups at these days. The activity of superoxiddismutase and catalase was significantly more than in control rats at the fourth day after stress.

Stress-induced changes in the liver of rats with different resistance to stress.

We compared changes in the liver structure in stress-resistant and stress-sensitive rats under conditions of chronic stress exposure. The number of degenerative cells, specific area of degenerative part of hepatocyte cytoplasm, and specific area of intralobular sinusoidal capillaries increased in animals of both groups. These parameters were significantly higher in stresss-ensitive rats. Reparative processes that manifested in increased in number of binucleated hepatocytes and number of nucleoli in nuclei were observed in the liver parenchyma. These changes were more pronounced in animals with high resistance to stress. Nucleus hypertrophy was also found in these rats.

[The influence of hepatocyte growth factor on lipid peroxidation processes in stress].

The influence of hepatocyte growth factor (HCF) on the activation of lipid peroxidation (LP) and activity of antioxidant enzymes in rat plasma was investigated in immobilization stress. It was established that investigated peptide decreases stress-induced activation of lipid peroxidation manifesting by the decrease of the content of intermediate and final metabolites of LP in plasma. HCF causes the increase of the activity of catalase (enzyme of antioxidant system) also, which decreased under stress influence.

Effects of regulatory peptides on the stress-induced changes of lipid metabolism in experimental animals.

Experiments on rats showed that restraint stress is associated with an increase in plasma level of nonesterified fatty acids, total cholesterol, triglycerides, VLDL, and LDL. Administration of opioid peptides DSLET and DAGO alleviated stress-induced shifts in lipid metabolism. The concentrations of nonesterified fatty acids, total cholesterol, and triglycerides decreased and HDL content increased under these conditions. Treatment with dynorphin A (1-13) prevented a significant increase in the concentration of nonesterified fatty acids in blood plasma, but did not affect the content of triglycerides and total cholesterol. Hepatocyte growth factor had minor influence on the analyzed parameters. The observed effects can be related to the stress-limiting effect of opioids, in particular, attenuation of catecholamine influence on the lipid tissue and generation of LPO products that inhibit cholesterol-degrading enzyme.

[Lipid peroxidation in the immobilization stress of different duration].

It was demonstrated in experiments on rats, that increase of immobilization stress duration causes more prolonged activation of lipid peroxidation, however significant differences of both malonic dialdehyde and acylhydroperoxides content were not established in early period after stress in rats, which were exposed to the immobilization of different duration. It was shown, that increase of superoxiddismutase activity is observed in early period of 3-hour and 6-hour stress, but it was decreased in 12-hour immobilization. Catalase activity was decreased in 6-hour and 12-hour stress. These results confirm the literature data about dependence between the expression of stress manifestations and the strength and duration of stress factor action.

Effect of opioid peptides on the content of LPO products and antioxidant enzyme activity in the liver of rats after restraint stress.

Administration of opioid peptides dynorphin A (1-13) and DSLET was followed by a decrease in the stress-induced activation of LPO and increase in SOD activity in the liver tissue of rats. DAGO produced a similar, but less pronounced effect. The observed changes can be related to a specific distribution of opioid receptors in the liver tissue and stress-limiting influence of these peptides in the whole body.

[Opioid peptides effect on lipid peroxidation in long-term stress].

It was shown in rats, that injection of opioid peptides (dynorphin A (1-13), DSLET and DAGO) decreased the stress-induced activation of lipid peroxidation in liver tissue and plasma. Dynorphin A (1-13) manifested the most expressed antioxidant effect in liver tissue. It not only decreased lipid peroxidation metabolites concentration, but also increased superoxiddismutase and catalase activity. Other peptides did not interfere enzyme activity. The use of DSLET or DAGO increased the superoxiddismutase plasma activity. Dynorphin A (1-13) injection increased catalase activity, but not superoxiddismutase. These effects could be explained by peculiarities of opioid receptors spread in liver tissue and stress-limiting action of peptides in entire organism.

[Effect of opiod peptides on free radical oxidation in a bone regenerate after fracture].

Opioid peptides (DSLET and DAGO) stimulating bone tissue regeneration were studied for effects on content of free radical products in regenerate tissue from the region of leg fracture in mice at various terms of reparative osteogenesis. These opioids reduce concentration of malonic dialdehyde and dienic conjugastes in bone for 10 days after fracture.