Disorders of the Biochemical Composition of the Periodontium in Rats with Periodontitis and Chronic Pain Syndrome.

We analyzed the composition of the periodontal tissue in rats with experimental periodontitis and chronic pain syndrome. Chronic pain syndrome was induced by bilateral ligation of the sciatic nerve; experimental periodontitis was modeled by application of eight-shaped silk thread ligature to lower jaw incisors followed by its immersion into the periodontal groove and fixation with additional knots. A decrease in the concentration of oxyproline, glycosaminoglycans, and catalase activity and an increase in the content of malondialdehyde and acylhydroperoxides in the periodontal tissue were found in animals with experimental periodontitis throughout the experiment (7-21 days). In animals with chronic pain syndrome, modelling of experimental periodontitis led to more pronounced decrease in the concentration of oxyproline and glycosaminoglycans, increase in the content of acylhydroperoxides and malondialdehyde, as well as a decrease in catalase activity in the periodontal tissue.

Correction of Lipid Metabolism Disorders in Diabetes Mellitus with Peptide Drugs.

We studied the effect of peptide drugs deltalicin and Semax on lipid metabolism disturbances in diabetes mellitus. Diabetes mellitus was modeled by single injection of streptozotocin (45 mg/kg) and rats with blood glucose ≥12 mmol/liter were selected for the further experiments. Deltalicin in a dose 100 µg/kg and Semax in a dose 200 µg/kg as well as sulodexide corrected lipid metabolism disorders: the content of total cholesterol, triglycerides, LDL, index of atherogenicity decreased and HDL concentration increased. Deltalicin produced more potent effect on lipid metabolism in rats with diabetes mellitus than sulodexide and Semax, which manifested in a significant decrease in total cholesterol and LDL concentration and index of atherogenicity.

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.

Effects of Melatonin on Stress-Induced Changes in the Liver of Rats with Different Resistance to Stress.

Effects of melatonin on changes in the liver structures were studied in stress-resistant and stress-sensitive rats exposed to chronic stress. It was found that the number of degenerative cells increased and intralobular sinusoidal capillary enlarged in the liver of animals of both groups. These parameters were significantly higher in stress-sensitive rats. Melatonin (1 mg/kg) reduced the severity of degenerative changes and stimulated the development of reparative processes in the liver tissue. The effects of the hormone was more pronounced in rats sensitive to stress and was noted after melatonin administration in a dose of 0.2 mg/kg.

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.

Effect of a synthetic indolicidin analogue on lipid peroxidation in thermal burns.

Experimental simulation of burn was followed by accumulation of LPO products and suppression of antioxidant enzyme activity in the burn wound. Application of a synthetic analogue of indolicidin led to an increase in MDA and acylhydroperoxide concentrations in the burn wound on experimental day 1. Further application of the peptide in a dose of 100 mg/kg had no significant effect on the studied parameters, while the peptide in a dose of 500 mg/kg was followed by a decrease in the level of LPO products on days 10 and 14. Changes in antioxidant enzyme activities in rats treated with 500 mg/kg indolicidin analogue had a two-phase pattern: an increase on day 4 was followed by a decrease.

[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.

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.