Dynamic Parameters and Cytokine Oxidative Homeostasis during Diatsereyin Treatment in Patients with Osteoarthritis and Comorbid Diseases

Tanas O. V., Khukhlina O. S.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Introduction. Osteoarthritis (OA) is a form of joint disease which affects 10­20 % of the population [8]. It is known that OA is often associated with arterial hypertension (AH) and obesity and these diseases have common pathogenetic mechanisms[2,4]. Important role in the pathogenesis of OA plays initiation of lipid peroxidation (LPO) [4], which results in the release of proinflammatory cytokines, especially interleukin (IL)­1β, IL ­6, tumor necrosis factor ­α (TNF ­α), breach of microcirculation, collagen structure and progression of degenerative joint process [4,5,9]. Modern clinical practice is based on an integrated approach to the treatment of OA. Prescription of drugs that have not only a symptomatic effect, but structure – modifying action in OA reduces the severity of pain and the need for analgesic therapy, increase compliance of the patients. Diatsereyin has such features [3,9]. It stimulates the synthesis of proteoglycans and hyaluronic acid with glycosaminoglycans, reduces signs of inflammation in the synovial membrane and lessens cartilage damage. Objective. To evaluate the efficacy of diatsereyin in the clinical course of osteoarthritis of the knee with comorbid hypertension and obesity, cytokine profile and parameters of pro­oxidant and antioxidant homeostasis. Materials and methods. The study included 24 patients (5 men and 19 women) with osteoarthritis of the knee, stage II­III with essential hypertension, stage II and class I obesity. The mean age of patients was 66,3 ± 5,7 years. To reduce pain they used non­steroidal anti­inflammatory drugs (NSAIDs). NSAIDs admission was situational and lasted for 5­7 days. Besides NSAIDs patients had diet after Pezner № 10, antihypertensive drugs to correct blood pressure from a group of ACE inhibitors and diatsereyin 1 capsule (50 mg) after meal in the evening for 2 weeks. Starting from the 2nd week of treatment, the dose was increased to 100 mg daily and divided in 2 doses (1 capsule in the morning and 1 in evening after meals), the treatment duration was 90 days. The effectiveness of treatment was evaluated by the following parameters: assessment of pain by visual analogue scale (VAS) and the index WOMAC. Blood levels of molecular products of lipid peroxidation (LPO) – isolated double bonds (IPZ) in compounds of diene conjugates (DC) were studied by a methodic after I. A. Volchehorsky et al., malonic aldehyde levels (MA) in plasma and erythrocytes by a methodic after Y. A. Vladimirov, A. Archakov. Blood levels of reduced glutathione (GSH) was determined by the titration method after O. Travin, with a modification by I. F. Meshchyshen, I. V. Petrova. Blood levels of cytokines : IL ­1β, IL ­6, TNF ­α, transforming growth factor ­β (TGF ­β) were determined by ELISA. Evaluation of the above parameters was performed before treatment and after 12 weeks of treatment. Statistical data processing were carried out using parametric methods of variation statistics. Results. The results showed that the treatment of OA patients with hypertension and obesity was significantly elevated blood levels of proinflammatory cytokines: IL ­1β – 1.5 ­fold (p < 0.05), IL ­6 – 1.5 times (p < 0.05), TNF ­α – 1. 5 ­fold (p < 0.05), which correlated with an increase of blood C­reactive protein 4.2 times (p < 0.05), content blood terminal : MA 1.9 times (p < 0.05) and intermediate products of lipid peroxidation. However, in these patients was set reduced blood levels of TGF ­β1 by 1. 7 times (p < 0.05). The latter fact indicates inhibition of proliferation of chondrocytes and production of collagen II, proteoglycan in cartilage. Purpose of combined therapy with the inclusion of diatsereyin led to a significant reduction in the intensity of pain after 7 days of treatment (the patients had a half dose), increased mobility of the affected joints after 10 days of treatment with complete abolition of NSAIDs. C­ reactive protein levels significantly decreased after treatment in 2. 6 times (p < 0.05), blood levels of lipid peroxidation products decreased significantly: MA 21. 4 % (p < 0.05), IPZ – by 31.7 % (p < 0.05), DC – 36.4 % (p < 0.05) with a simultaneous increase in the content of the erythrocytes GSH : 20.0 % (p < 0.05), which indicates a reduction in the intensity of oxidative stress and restoration potential for chondrocytes regeneration. Along with this, diatsereyin has impact on blood levels of proinflammatory cytokines: singinificantly reduced the content of IL ­1β – on 29.3 % (p < 0.05) with normalization of IL­ 6 – 25.9 % (p < 0,05), TNF ­α – 26,0 % (p < 0.05). The mechanism of diatsereyin anti­inflammatory action is not caused by influence on COX and lipoxygenase. Basic pathogenetic diatsereyin effect and its active metabolite reyine in OA is blocking the synthesis of IL­ 1 [9], inhibition of the expression of receptors for it on the chondrocytes surface, thereby reducing the sensitivity of cells to the action of this cytokine. Intracellular metabolite blocks the activation and translocation of the NFκB in the nucleus, reducing the expression of NFκB – dependent genes, including responsible for production of proinflammatory cytokines: TNF ­α, IL ­1β, IL ­6, nitrogen monoxide and metalloproteinase, contributing to enhanced destruction of components in cartilage matrix [9,10]. However, combined therapy resulted in normalization of blood levels of TGF ­β1 up to 2.0 times (p < 0.05), which probably contributes to the restoration of proteoglycan biosynthesis in cartilage and restores regeneration process in the cartilage itself. Conclusion. The inclusion of a comprehensive treatment of osteoarthritis in the background comorbidity of obesity and hypertension diatsereyinu facilitates rapid elimination of pain in the affected joints, increase their mobility, inhibition of inflammation, reduce the intensity of oxidative stress and inhibition of cytokine level regulation of inflammation by neutralizing the action of proinflammatory cytokines : IL ­1β, IL ­6, TNF ­α and restoration potential stimulant of cartilage regeneration (TFRβ1). Prospects for future research are to study the impact Diatsereyin the clinical course of comorbid diseases: hypertension and obesity.

Osteoarthritis, arterial hypertension, obesity, cytokines, oxidative stress

«Bulletin of problems biology and medicine» Issue 3 part 2 (111), 2014 year, 241-244 pages, index UDK 616. 72–007. 24: 616. 12–008. 331. 1]–056. 257­002–092: 577. 121