LAUSR

Background: MOG system is present not only in the liver but also in far less quantities in other organs and tissues, including SF. Objectives: SF in RA patient contains up to 95% of NL that determines the inflammation also by inhibiting MOG. Methods: SF of knee joints of 8 patients with RA with active synovitis and 4 donors (D) were examined. NL have been isolated by standard methods. After the application of Triton-X-100 0,1% solution, NL has been centrifuged at 25000 g for 30 minutes. The supernatant has been used in the experiment. The activity of MOG has been estimated according to the level of cytochromes P450. P420 and b5 have been estimated by applying the method of differential spectrophotometry. Active forms of oxygen have been registered by applying electron paramagnetic resonance (EPR). The activity of the antioxidant enzymes - Cu-Zn superoxiddismutase (Cu-Zn SOD), Se-glutathione peroxidase (Se-GPO) and catalase (CAT) was estimated by employing classical enzymology methods. Results: It has been found out that in RA, the level of active oxygen forms increases by 68%. Meanwhile, the enzymes level of antioxidant defense is insufficient. In RA the activity of SOD, GPO and CAT enzymes is inhibited at 52, 66 and 39% respectively. In RA the activity of MOG (P450 and b5) in NL is 4 times lower than normal. The concentration of the inactive form of cytochrome P420, however, doubles. Nevertheless, their ratio P450/P420 (when normal = 5) in case of RA = 5,6 hardly ever changes. Cytochrome concentration P450, P420 and b5 (nmol/g of protein), level of active oxygen forms (Units/mg of protein) and antioxidant system activity (SOD, GPO - Units/mg of protein; CAT- μmol/min·mg of protein) in NL in RA NL P-450 P-420 b5 Level of active forms Cu-Zn SOD Se-GPO CAT D 1,25 ± 0,4 0,025 - 0,029(0,027) 0,43±0,07 15,7 ± 4,1 19,7 - 34,4(27,1) 1,8 - 2,3(2,1) 10,8 - 15,3(13,1) PA 0,3 ± 0,1 0,054 - 0,063(0,058) 0,11±0,03 49,4 ± 8,6 10,7 - 15,3(13.1) 0,6 - 0,8(0,7) 0,76 - 0,84(0,8) Conclusion: A fall in the level of free radical oxidation and antioxidant defense and faster generation of active oxygen forms in RA leads to NL being destroyed and creates favorable conditions for the development of autophagy and apoptosis. The oxidative stress during RA is accompanied by a fall in the activity of MOG and activation of lipid peroxidation and cytokine production in NL as shown earlier. A general fall in the activity of MOG (P-450 and b5) in NL in RA occurs against the background of enhanced conversion of P-450 into the inactive cytochrome P-420. This fact proves that the expression of isoenzymes P450s (CYPs) is reprogrammed whilst the autoimmune pathology is being developed and there is an unbalance of the immune oxygenase homeostasis in RA. Reference [1] Shishkin V. I. et al. Ann Rheum. Dis. 2016;75: sup.2 - 5832. Disclosure of Interests: None declared