INFLUENCE OF NESTEROID ANTI-INFLAMMATORY DRUGS AND PARACETAMOL ON THE LEVEL OF INTERLEUKINS OF RAT BLOOD SERUM UNDER CONDITIONS OF EXPERIMENTAL HYPOTHYROIDISM AND OSTEOARTHRITIS
About the author:
Nosivets D. S.
CLINICAL AND EXPERIMENTAL MEDICINE
Type of article:
The article investigated changes in the level of interleukins under the influence of non-steroidal antiinflammatory drugs and paracetamol under experimental equivalents of hypothyroidism and osteoarthritis. To date, there is a clear need to identify biomarkers that could predict a patient’s response to osteoarthritis treatment, primarily in comorbid conditions. It is known that hypofunction of the thyroid gland leads to metabolic disorders that negatively affect the condition of bone and cartilage, causing the development of osteoarthritis. One manifestation of osteoarthritis is considered to be a pathological change in the subchondral bone, which responds to the disease by the formation of sclerosis, marginal bone growths and the formation of deformation of the joint surfaces due to the destruction of bone tissue. Although NSAIDs are effective in reducing pain and disability in patients with osteoarthritis, it is still unclear to what extent these drugs can affect joint metabolism and, therefore, joint structure, especially against the background of functional thyroid insufficiency. The experiments were carried out on 70 white outbred rats of both sexes, which recreated osteoarthritis and hypothyroidism. Experimental osteoarthritis was performed by single intra-articular administration of 0.1 ml of monoacetic acid solution in the knee joint, which was prepared at a rate of 3 mg of the reagent on 50 μl of sterile physiological saline. Experimental hypothyroidism was reconstructed by enteral administration of a 0.02% solution of carbimazole, which was prepared at a rate of 5 mg per 250 ml of physiological solution and given with a drinking ration of animals for 6 weeks. The adequacy of the model was confirmed by the level of serum TSH, T3 and T4 in rats. After the formation of the experimental models on the 42nd day of the experiment, the animals were divided into 14 groups and drug administration began daily for 5 days. The quantitative level of interleukins of blood serum was determined by competitive in vitro ELISA twice on 42 and 47 days of the experiment. Blood samples were obtained from the rat tail vein by puncture using a vacuum system at 42 and 47 days of the experiment. Statistical data processing was performed using the Statistica 6.1 software package (StatSoftInc., Serial number AGAR909E415822FA) and included calculations of arithmetic mean values (M) and their errors (± m). The probability of the difference between the arithmetic mean (p) values of the indices was made using non-parametric – U-criterion Mann-Whitney. The determination of the probability of intragroup and intergroup differences was performed using the parametric t-criterion of the Student and the method of single-factor dispersion analysis (ANOVA). Differences were considered statistically significant at p≤0.05. Based on the study, it was found that determining the level of interleukins allows to evaluate the anti-inflammatory activity NSAIDs against the background of experimental equivalents of osteoarthritis and hypothyroidism. The data obtained from rat’s serum interleukins reflects the extent of the effects of NSAIDs and paracetamol due to the interaction of drugs in experimental osteoarthritis and hypothyroidism. According to the degree of influence on degenerative-dystrophic processes in bone tissue the investigated drugs can be arranged as follows: diclofenac sodium > ibuprofen > nimesulide = meloxicam > celecoxib > paracetamol.
osteoarthritis, hypothyroidism, NSAIDs, pharmacotherapy, biochemical markers, interleukins 1 and 6
- Nosyvets DS. Vlyianye funktsyonalnoi nedostatochnosty shchytovydnoi zhelezi na kostno-khriashchevuiu tkan. Morfolohyia. 2019;1(13):47- 51. [in Russian].
- Graham RW. Thyroid hormone actions in cartilage and bone. Eur Thyroid J. 2013;2:3-13.
- Nosyvets DS. Vlyianye kombynatsyy NPVS na techenye osteoartroza pry soputstvuiushchem hypotyreoze. Problemi endokrynnoi patolohyy. 2019;2(68):40-5. [in Russian].
- Nosivets DS. Mozhlyvist sumisnoho vykorystannia L-tyroksynu, dyklofenaku natriiu ta khondroitynu sulfatu pry hipotyreozi. Visnyk problem biolohii i medytsyny. 2019;2,1(150):172-6. [in Ukrainian].
- Mobasheri A, Bay-Jensen AC, Spil WE, Larkin J, Levesque MC. Osteoarthritis year in review 2016: biomarkers (biochemical markers). Osteoarthritis and Cartilage. 2017;25:199-208.
- Nosivets DS. Eksperimentalnyie modeli patologii hryaschevoy tkani. Zaporozhskiy meditsinskiy zhurnal. 2019;21,4(115):554-60. [in Russian].
- Guingamp C, Gegout-Pottie P, Philippe L. Mono-iodoacetate-induced experimental osteoarthritis: a dose-response study of loss of mobility, morphology, and biochemistry. Arthritis Rheum. 1997;40(9):1670-9.
- Argumedo GS, Sanz CR, Olguín HJ. Experimental models of developmental hypothyroidism. Horm Metab Res. 2012;44:79-85.
- Poloz AI, Finogenov AYu. Metodicheskie ukazaniya po gumannoy evtanazii zhivotnyih. Minsk, 2008. 45 s. [in Russian].
- Mironov AN, redaktor. Rukovodstvo po provedeniyu doklinicheskih issledovaniy lekarstvennyih sredstv. Ch. 1. M.: 2012. 944 s. [in Russian].
- Kostyuk VO. Prikladna statistika: navch. posibnik. H.: HNUMG im. O.M. Beketova; 2015. 191 s. [in Ukrainian].
- Balabanova RM. Rol interleykina 1 pri osteoartroze i vozmozhnosti ego blokirovaniya. Sovremennaya revmatologiya. 2011;1:58-62. [in Russian].
- Shirinskiy VS, Kazyigasheva EV, Shirinskiy IV. Vospalenie i imunitet: rol v patogeneze osteoartrita. Meditsinskaya imunologiya. 2019;21,1:39- 48. [in Russian].
- Starodubtseva IA, Vasileva LV, Nikitin AV. Korrektsiya vospalitelnogo protsessa s pomoschyu ingibitora interleykina-1 v kompleksnom lechenii vtorichnogo osteoartroza na fone komorbidnoy patologii. Terapevticheskiy arhiv. 2015;12:41-8. [in Russian].
- Yin J, Huang Y, Gao G, Nong L, Xu N, Zhou D. Changes and significance of inflammatory cytokines in a rat model of cervical spondylosis. Еxperimental and therapeutic medicine. 2018;15:400-6.
- Raskina TA, Letaeva MV. Novyiy vzglyad na problemu terapii osteoartroza. Sovremennaya revmatologiya. 2012;4:86-9. [in Russian].
- Kopyilova DA, Ostapenko VA. Svyaz klinicheskih proyavleniy osteoartroza s izmeneniem urovnya interleykina 6 v krovi. Nauch-praktich revmatol. 2012;54(5):34-6. [in Russian].
- Heinrich PC, Castell JV, Andus T. Interleukin 6 and the acute phase response. Biochem J. 2006;265:621-36.
- McGee DW, Beagley KW, Aicher WK, McGhee JR. Transforming growth factor-beta and IL-1 beta act in synergy to enhance IL 6 secretion by the intestinal epithelial cell line, IEC-6. J Immunol. 2003;151:970-8.
- Paquet J, Goebel J-C, Delaunay C, Pinzano A, Grossin L. Cytokines profiling by multiplex analysis in experimental arthritis: which pathophysiological relevance for articular versus systemic mediators? Arthritis Research and Therapy. 2012;14(2):60.
- Rainsford KD, Ying C, Smith FC. Еffects of meloxicam, compared with other nsaids, on cartilage proteoglycan metabolism, synovial prostaglandin e2, and production of interleukins 1, 6 and 8, in human and porcine explants in organ culture. J Pharm Pharmacol. 1997;49(10):991-8.
- Henrotin YE, Labasse AH, Simonis PE, Zheng SX, Deby GP, Famaey JP, et al. Effects of nimesulide and sodium diclofenac on interleukin-6, interleukin-8, proteoglycans and prostaglandin E2 production by human articular chondrocytes in vitro. Clin Exp Rheumatol. 1999;17(2):151- 60.
- Bianchi M, Broggini M, Balzarini P, Franchi S, Sacerdote P. Effects of nimesulide on pain and on synovial fluid concentrations of substance P, interleukin-6 and interleukin-8 in patients with knee osteoarthritis: Comparison with celecoxib. Int J Clin Pract. 2007;61(8):1270-7.
Publication of the article:
«Bulletin of problems biology and medicine» Issue 1 (155), 2020 year, 175-179 pages, index UDK 615.017