APPLICATION OF QUERCETIN FOR CORRECTION OF THE IMPAIRMENT OF THE FUNCTIONAL STATE OF THE ENDOTHELIUS OF VESSELS (CLINICAL AND EXPERIMENTAL STUDY). / ZASTOSUVANNIa KVERTsETYNU DLIa KOREKTsIÏ PORUShEN' FUNKTsIONAL'NOGO STANU ENDOTELIIu SUDYN (KLINIKO-EKSPERYMENTAL'NE DOSLIDZhENNIa).

OBJECTIVE: in the experiment, to investigate the effect of Quercetin on the NO-dependent reactions of isolated vessels involving endothelium and perivascular adipose tissue (PVAT) after a single X-ray irradiation of rats at a sublethal dose. In a clinical study, to investigate the effect of long-term use of Quercetin on the functional state of themicrovascular endothelium in the elderly patients with metabolic syndrome (MS). MATERIAL AND METHODS: Experimental studies were performed on vascular fragments obtained from adult male rats(7-8 months) of the control group, in animals exposed to a single R-irradiation at a dose of 7 Gy and animals irradiated in the same dose, which received Quercetin orally for 14 days three times a week based on 10 mg/kg bodyweight. Fragments of the thoracic aorta (TA) and mesenteric artery (MA) were cleaned of perivascular adipose tissue (PVAT-) or left uncleaned (PVAT+), and then were cut into rings (up to 2 mm). The amplitude of the contractionof the rings TA and MA under the influence of phenylephrine (PE, 3 x 10-6 M), the amplitude of the contraction of therings TA and MA in the presence of a competitive blocker of NO-synthase methyl ester of N-nitro-L-arginine(L-NAME, 10-5 M), the amplitude of relaxation of the rings TA and MA in the presence of N-acetylcysteine (NAC, 10-4 M)were measured. The clinical study examined 110 patients with MS criteria in accordance with ATP III (2001).Patients in the main group for 3 months received Quercetin from the same manufacturer, 80 mg three times a day,patients in the control group received placebo. RESULTS: Single R-irradiation disrupts the regulation of the contractile function of TA and MA, which is evidenced bychanges in the contractile reactions of isolated fragments of these vessels as a response to the action of vasoactivecompounds. Course use of Quercetin in irradiated rats leads to the normalization of contractile and dilatory vascular responses due to partial correction of NO metabolism in the endothelium and PVAT. For the majority of patients(69 %) who received Quercetin, a post-occlusive hyperemia test showed a statistically significant increase of maximal volumetric velocity of the skin blood flow rate and duration of the recovery period to the baseline, which indicates about improvement of vasomotor vascular endothelial function. CONCLUSIONS: Course use of Quercetin improves the functional state of the microvascular endothelium among theelderly people with MS, normalizes contractile and dilatory vascular responses in irradiated rats due to partial correction of NO metabolism in the endothelium and PVAT.

[Influence of liposomal glucosaminyl-muramyl dipeptide on superoxide and nitric oxide production by murine macrophages].

Reactive oxygen and nitrogen intermediates are key factors in inflammatory response and antitumoral activity of macrophages. Free and liposomal N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D-isoglutamine influence on murine macrophages ability to generate superoxide and nitric oxide were studied. The cells pretreated by GMDP increased superoxide generation in response to secondary stimuli (phorbol ether, lipopolysaccharide, zymosan). Encapsulation in the egg phosphatidylcholine liposomes enhanced cell sensitivity to priming effect of GMDP. The presence of liposomes (up to 0.5 mg/ml) in the medium inhibited superoxide release by macrophages probably due to participation of NO as redox-active metabolite. GMDP (up to 50 microg/ml) alone as well as GMDP with LPS treatment stimulated nitric oxide synthesis by macrophages. Liposomal GMDP at lower concentrations (up to 0.02 microg/ml) enhanced macrophage response to LPS. In contrast, NO-synthetic activity of LPS-stimulated cells decreased along with the increase of liposomal GMDP concentration (up to 0.5 microg/ml). The conditions for effective use of liposomal GMDP in immunotherapy are discussed.