Yelins'ka A. NO- and NF-кB-dependent mechanisms affecting salivary glands in rats under modeled metabolic syndrome

This dissertation is devoted to solving the problem which consists in the determining the role of NO-system components (different isoforms of NO-synthase, its substrate, peroxynitrite) and transcription nuclear factor ?B in the pathogenesis of functional and metabolic disorders of submandibular salivary glands (SG) in rats under modeled metabolic syndrome (MS). This work has demonstrated the modeling of MS in SG tissues results in reciprocal changes in oxidative (mainly, NO-synthase way due to iNOS hyperactivation) and non-oxidative (arginase) metabolic pathways of L-arginine and enhancing the total production of anion-radical superoxide (О ) production, and its generation by mitochondrial and NADPH-dependent electron transport chains (microsomal and NOS) with following activation of processes of lipid peroxidation and reducing of antioxidant (AO) potential. It has been found out the functional activity of nNOS in modeled MS reduces the О production by NADPH-dependent and NADH-dependent electron transport chains (ETC), limits lipid peroxidation, but does not suppress the catalase activity and does not affect sufficiently on AO potential SG tissues. Functioning of nNOS in modeled MS promotes the growth of ?-amylase activity in the tissues of submandibular SG. This research has revealed the imbalance of NOS and arginase ways of L-arginine metabolism and activation of free-radical reactions in the tissues of submandibular SG in modeled MS is caused by peroxynitrite-dependent as well as NF-?B-dependent processes. The introduction of peroxynitrite scavenger L-selenomethionine and NF-?B activation inhibitors as JSH-23 and metformin hydrochloride under the experimental MS lowered NOS activity, О production by NADPH-dependent and NADH-dependent (mitochondrial) ETC, limited lipid peroxidation activity and increased of AO protection in the SG tissues. L-selenomethionine introduction and an inhibitor of nuclear translocation NF-?B JSH-23 (4-methyl-N-(3-phenylpropyl)benzene-1,2-diamine) under experimental conditions improves protein- synthesizing function by submandibular SG that is far from being typical when metformin hydrochloride is administered.