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Fig. 4. Radiographs of the patient before operation
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Shukurova Umida Abdurasulovna, PhD, Tashkent State Dental Institute, Uzbekistan, Faculty Dental Therapeutics department E-mail: [email protected] Bekjanova Olga Esenovna, PhD, MD, DDS, Faculty Dental Therapeutics department E-mail: [email protected]
Role of oxidative process in pathogenesis of oral lichen planus
Abstract: Imbalance between free radical oxidation and anti-oxidant system is one of the key links of development of lichen planus on oral mucosa. Data on evaluation of anti-oxidant system (AOS) and peroxidation of lipids (POL), degree of imbalance between pro- and anti-oxidants in biological substratum (blood, oral liquid) are sensitive and objective indices of severity of pathologic processes on oral mucosa, that proves use of antioxidants in complex treatment of oral lichen planus (OLP) as local and system cure.
Keywords: lichen planus, oral liquid, lipid peroxidation, anti-oxidant system, diene conjugates, trienoic conjugates, malonic conjugates, catalase, superoxide dismutase, glutathione peroxidase.
Lichen planus (LP) is inflammatory, immune dependant disease of skin and oral mucosa, which is characterized by chronic polymorbid clinical current, torpidity to traditional therapy ad polymorphism of clinical manifestation [4, 3-4; 5, 267; 6, 57-58; 7, 11; 9, 55-57; 10, 7-8; 11, 300-301; 16, 683-684].
It should be noted, that OLP often has severe clinical current, at the same time one form could transform into another one, and malignancy frequency is equal to 6-7 % [13, 682; 15, 458-459].
Nowadays there is no doubt that pathogenesis of OLP is germane to development of oxidative stress, which can become the
reason of immune insufficiency and can cause chronic pathologic process [3, 106-107; 6, 58; 12, 355-357; 14, 311].
In spite of large number of studies in this field, questions of state of POL-AOS in patients with the different clinical forms of OLP remain uncertain, the importance of clinical research of state of this mechanisms on local "oral liquid" and system "blood" levels has not been established till the end.
In view of aforesaid the purpose of research is to study processes of free radical oxidation (FRO) of oral liquid and blood serum in patients with different clinical forms of OLP.
Section 6. Medical science
Material and methods
107 patients with exacerbation of OLP, including 27 patients with typical form, 34 patients with exudative-hyperemic form, 32 patients with erosive-ulcerous form and 14 patients with bullous form, were examined. Control group was presented 20 patients of commensurable gender and age, without diseases of skin and oral mucosa. Compared groups were randomized by gender and age, which provided representativeness of received data.
The level of POL processes was evaluated on consistence of diene conjugates (DC) as primary products of lipid peroxidation, tri-enoic conjugates (TC) and malonic conjugates (MC) as secondary products and Schiff bases (SB) as final product. Content of DC, TC and SB was estimated as correlation of transmission density of lipid extracts accordingly E232/E220; E278/E220 and E400/E220 and evaluated in conventional units, isopropanole fraction was considered. MDA concentration was evaluated by spectrophotometric method in test with thiobarbituric acid (Konyukhova V S., 1989).
State of AOS processes was estimated on activity of antioxi-dant enzymes, such as catalase (CT) (Korolyuk M. A. etal 1988); superoxide dismutase (SOD) (Nishikimi N. et al., 1972); glutathione peroxidase (GP) (B. Paglia, W. Walentine, 1967); and activity of succinate dehydrogenase (SuDH) (Storozhuk P. G. and Storozhuk A. P., 2003).
Statistical treatment was carried out on personal computer with the use of «Microsoft Excel» program, we estimate mean value M, standard error of mean value-m; reliability of differences was evaluated on the base of t, Student criterion.
Results and discussion
It is established from data analysis that chronic inflammatory process on oral mucosa is characterized by apparent activity of POL processes and exhaustion of endogenous anti-oxidant potential. In comparing of activity of studied processes higher values of studied indices were noted in oral liquid, which reflected activity of local process on mucous membranes, and higher activity of metabolic processes in oral cavity.
The increase of concentrations of studied POL processes progressively growing with the increase of severity of pathologic process was registered in oral liquid and in blood serum.
Thus, in oral liquid DC concentration was increased on 37.73 % (P < 0.01) in typical form of OLP; 83.36 % (P < 0.001) in exuda-tive-hyperemic form; 119.09 % (P < 0.001) in erosive-ulcerous and 112.73 % (P < 0.001) in bullous form; corresponding dynamics ofTC and MDA were equal to 23.81 % (P < 0.01) and 46.95 % (P < 0.01); 78.54 % (P < 0.01) — 83.33 % (P < 0.01); 151.25 % (P < 0.001) and 109.62 % (P < 0.01) and 175.61 % (P < 0.001) — 111.50 %
(P < 0.001); and SB was on 84.0 % (P < 0.01); 124.0 % (P < 0.01); 224.0 % (P < 0.01) and 232.0 % (P < 0.01) correspondingly (fig. 1).
Increase of POL processes on system level (blood serum) was less expressed. Thus in typical form of OLP level of DC was increased on 17.90 % (P < 0.05) concerning control one; TC and MDA were on 17.87 % (P < 0.05) and 36.65 % (P < 0.05); and SB was on Ha 75.0 % (P < 0.001); corresponding correlation in erosive-ulcerous form were 72.90 % (P < 0.01); 85.71 % (P < 0.001); 73.58 % (P < 0.01) and 125.0 % (P < 0.001); in bullous form they were 80.52 % (P < 0.01); 93.21 % (P < 0.001); 76.42 % (P < 0.01) and 112.5 % (P < 0.01) correspondingly (fig. 2).
Stable increase of DC concentration as product of early response is an evidence of constant maintaining increased activity of POL processes caused by pathologic process, and also of stable "infeed" of humoral environment of organism with fresh products of this type of metabolism
Changes of other indices of POL, such as TC and MDA level (intermediate product of POL), SB concentration (products of late response) less reflect activity of process characterizing involvement of different morphologic structures, cell membranes first of all, in lipid peroxidation.
In research of endogenous anti-oxidant potential asynchrony of activity of AOS enzymes was stated, clear increase of enzyme activity in biologic environment in typical and exudative-hyperemic forms changed into its decrease in patients with erosive-ulcerous and bullous forms.
Thus. in patients with typical form of OLP CT activity was increased on 32.61 % (P < 0.05); SOD was on 34.74 % (P < 0.01); GP was on 26.51 % (P < 0.05); and SuDH was on 22.21 % (P < 0.05); corresponding dynamics in exudative-hyperemic form was equal to 45.95 % (P < 0.01); 50.0 % (P < 0.01); 43.06 % (P < 0.01) and 67.40 % (P < 0.01); decrease of AOS enzyme activity in erosive-ulcerous form was 39.55 % (P < 0.01); 42.45 % (P < 0.01); 42.88 % (P < 0.01) and 48.75 % (P < 0.01); in bullous form it was 42.75 % (p < 0.01); 46.37 % (P < 0.01); 43.68 % (P < 0.01) and 49.67 % (P < 0.01) correspondingly (fig. 1).
Similar dynamics ofAOS enzymes in blood serum were presented: in typical and exudative-hyperemic forms as increase: CT was on 20.0 % (P < 0.05) and 35.45 % (P < 0.05); SOD was on 20.0 % (P < 0.05) and 39.24 % (P < 0.05); GP was 16.0 % (P < 0.05) and 22.02 % (P < 0.05) and SuDH was on 13.18 % (P>0.01) and 18.62 % (P < 0.05); in erosive-ulcerous and bullous forms corresponding decrease was on 31.33 % (P < 0.01) and 44.87 % (P < 0.01); 33.14 % (P < 0.01) and 38.1 % (P < 0.01); 27.8 % (P < 0.05) and 33.73 % (p < 0.01); 23.35 % (P < 0.01) and 25.65 % (P < 0.01) (Fig. 2).
Fig. 1. Indices of intensity of POL processes and AOS activity in oral liquid in patients with OLP (M ± m)
Fig. 2. The indices of intensity of POL processes and AOS activity in blood of patients with OLP (M ± m)
Reaction of free radical oxidation is initiated with active form of oxygen leading to chemical modification and destruction of bio molecules. In conditions of oxidative stress and intensive formation of active forms of oxygen disturbance of functioning of antioxidant enzymes occurs.
Catalase (CT) is enzyme of oxidoreductase class, included in cell antioxidant system content and realizing function of anti-peroxide protection (H2 02); glutathione peroxidase (GP) is catalyst for reducing reaction of hydrogen peroxide (H2 02) lipid hydro-peroxide (ROOH); superoxide dismutase (SOD) realizes catalysis of recombination reaction of superoxide anions (02-); succinate dehydrogenase (SuDH) is enzyme of oxidoreductase class, it is localized in inner membrane of mitochondria and is one of important enzymes of energetic exchange, catalysts reversible oxidation of siccine acid (suc-cinate) to fumaric acid in Krebs cycle of tricarboxylic acids. Oxidation of 1 mole of siccine acid leads to synthesis of 2 moles of adenosine triphosphate (ATP). Electrons from succinate dehydrogenase are sent to respiratory chain on coenzyme Q. Decrease of SuDH activity reflects decrease of cell endotransport respiratory chain [8, 14-15].
Quantitative characteristics of main energetic process in mitochondria, which is oxidation of siccine acid (OSA) and its signal operation characterize intensity of sympathetic (adrenergic) regulation in organism. OSA with SuDH is the most potent process of energy saving, which affects physiologic state of organism. SuDH activity as mitochondria enzyme is an important index of connection ofphysi-ologic state and mitochondrial processes [1, 220; 2, 29-30]. Decrease of SuDH activity in patients with erosive-ulcerous and bullous forms of OLP is evidence of need of reducing energetic mitochondrial processes medicines in complex treatment.
Thus, existed changes characterize different on direction, but compelled shifts in both links of prooxidant-antioxidant system
illustrating intensive imbalance. Increase of POL products concentration reflecting growth of FRO intensity contributes to faster exhaustion of bio antioxidant supplies and reduction of system redox potential. In this case peculiar "vicious circle" is formed, when every previous stage starts following one, and probability of state reversibility and normalization gradually decreases till minimum. Results unambiguously confirm that generalization and intensity growth of OLP cause gradual exhaustion of physiologic supply of bio antioxidants. Relative increase of AOS enzymes in patients with typical and exudative-hyperemic forms lets to consider volume increase of protective physiologic antioxidant systems for regulation of POL processes. In change to bullous and erosive-ulcerous forms "qualitative leap" occurs, when reserve power of antioxidant system is not enough for compensation of increased POL processes, stimuli correlation changes toward pro-oxidant agents and oxidative destruction contributes to developed pathologic process on oral mucosa.
Imbalance of homeostasis manifests with emaciation and frustration of antioxidants of direct action eliminating free radicals and enzymes of cell energetic supply having direct and indirect effects.
Thus, imbalance between free radicals peroxidation and AOS is one of the key links of development of OLP.
Data on evaluation of POL-AOS processes, shift degree between pro- and anti-oxidants in biological substrates (blood, oral liquid) are sensitive and objective indices of severity of pathologic process on oral mucosa, substantiating need of antioxidants in complex treatment of OLP as local and system cure.
Increase of cell energetic potential, which allows to maintain energosynthetic function of mitochondria in condition of progressive hypoxia, should be considered as perspective way.
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