This dissertation aimed at determining the role of neuronal and inducible NO-synthase (NOS), peroxynitrite and nuclear factor kB (NF-kB) in the mechanisms of periodontal tissue damage in rats exposed combined toxic effects of sodium nitrate and sodium fluoride. The research has demonstrated for the first time that the combined intragastric administration of sodium nitrate (in a dose of 200 mg/kg of body weight) and sodium fluoride (in a dose of 10 mg/kg of body weight) for 30 days results in dysregulation changes in the activity of enzymes of oxidative (NO-synthase) and non-oxidative (arginase) L-arginine metabolic pathways in the periodontal soft tissue. Inhibition of NOS total activity that is typically observed at separate sodium nitrate administration turns into their hyperactivity accompanied by increasing in the concentrations of peroxynitrite; while arginase activity and ornithine decarboxylase significantly reduces. Under these conditions there is potentiation in the production of superoxide anion radical (SAR) by NADPH-dependent electron transport chains (microsomal and NOS), by NADH-dependent mitochondrial respiratory chain, as well as an increase in its generation by NADPH oxidase of leukocytes, increased lipid peroxidation and collagenolysis in soft periodontal tissues, and increased resorption of alveolar processes of the jaws. To assess differences in the effects of NOS isoforms, the test rats were administered 7-nitroindazole (in a dose of 30 mg/kg), a selective inhibitor of neuronal NO-synthase (nNOS), and aminoguanidine (20 mg/kg), a selective inhibitor of inducible NO-synthase (iNOS), intraperitoneally twice a week for a 30-day period of combined exposure to nitrate and sodium fluoride. It has been shown the functional iNOS activity under combined intoxication with nitrate and sodium fluoride inhibits the enzymes of arginase pathway of L-arginine metabolism in the periodontal soft tissues, promotes the production of SAR by NADPH- and NADH-dependent electron transport chains and by NADPH-oxidase of leukocytes, as well as enhances the activation of decompensated lipid peroxidation and lowers antioxidant potential. The research has revealed the differences in the effects of nNOS and iNOS on periodontal connective tissue disruption under combined intoxication with nitrate and sodium fluoride. It has been found out the functional activity of nNOS in these conditions limits collagenolysis in soft periodontal tissues and depolymerization of proteoglycans in the tissue of alveolar process of the jaws. The functional activity of iNOS, on the contrary, increases collagenolysis and proteoglycans depolymerization in soft periodontal tissues, increases resorption of alveolar processes of the jaws. It has been established the administration of L-arginine for combined 30-day exposure to nitrate and sodium fluoride increases arginase activity in soft periodontal tissues, reduces the production of SAR by respiratory mitochondria chain and by NADPH oxidase of leukocytes, limits lipid peroxidation, elevates the activity of catalase, and reduces proteoglycans depolymerization in the bone tissues, as well as reduces resorption of alveolar processes of the jaws. L-selenomethionine (in a dose of 3 mg/kg, twice a week) and uric acid (in a dose of 250 mg/kg, 3 times per week) have been proven to be effective peroxynitrite scavengers in soft periodontal tissues in simulated chronic intoxication with nitrate and sodium fluoride; they reduce the total activity of NOS, as well as they decrease peroxynitrite concentration. The use of L-selenomethionine under these conditions increases ornithine decarboxylase activity, reduces the production of SAR by NADPH- and NADH-dependent electron transport chains, and by NADPH oxidase of leukocytes, limits lipid peroxidation, increases antioxidant capacity, reduces collagenolysis and proteoglycans depolymerization in bone tissue and soft tissues, loweres resorption of alveolar processes in the jaws. Administration of uric acid impedes the generation of SAR by mitochondrial respiratory chain in the soft periodontal tissues, limits lipid peroxidation, increases the activity of catalase, reduces collagenolysis, and hinders resorption of alveolar processes in the jaws. It has been found for the first time the introduction of JSH-23, an inhibitor of NF-kB activation (in a dose of 1 mg/kg, twice a week) in simulated combined chronic intoxication with nitrate and sodium fluoride reduces total activity of NOS in soft periodontal tissues, increases ornithine decarboxylase activity, hinders their production of SAR by NADPH- and NADH-dependent electron transport chains, and by NADPH oxidase of leukocytes, restricts the activity of lipid peroxidation, enhances antioxidant capacity, as well as reduces collagenolysis and proteoglycans depolymerization in both soft and bone periodontal tissues, reduces resorption of alveolar processes in the jaws.
