Some aspects of the therapeutic effect of dental gel with IL-1β antagonist in experimental chronic generalized periodontitis

Abstract

The aim of the current study was to evaluate the therapeutic efficacy of 1 % IL-1β antagonist dental gel by its effect on biomarkers of inflammation and cytoprotection under conditions of modelling chronic generalized periodontitis in rats.

Materials and methods. Chronic generalized periodontitis (CGP) was reproduced in Wistar rats weighing 180–210 g by 8-week administration of the prooxidant Delagil (chloroquine phosphate, 30 mg/kg) and addition of EDTA (2 %) to drinking water using a calcium-deficient peroxide diet with reduced chewing function. The studied pharmacological medications were administered after the development of CGP in rats for 30 days: 1 % oromucosal gel with IL-1β receptor antagonist (RAIL-1β, 1 mg/kg) locally using a dispenser; and the antioxidant Mexidol (250 mg/kg) intragastrically for 30 days. The condition of periodontal tissues and the effect of the studied medications on the levels of inflammatory markers IL-1β, tumour necrosis factor alpha (TNF-α), matrix metalloproteinase-2 (MMP-2) and markers of endogenous neuroprotection hypoxia-induced factor 1-alpha (HIF-1α) and heat shock proteins (HSP₇₀) were evaluated using enzyme-linked immunosorbent assay (ELISA).

Results. Modelling of CGP in rats by 8-week administration of the prooxidant Delagil and addition of EDTA to drinking water resulted in typical manifestations of the disease: bleeding, hyperaemia, and swelling of the gums; tooth mobility; formation of gingival pockets up to 8 mm against the background of increased levels of inflammation markers (TNF-α, IL-1β), and molecular markers (HIF-1α and HSP₇₀) in the blood indicated a homeostatic response of the periodontium to inflammation and subsequent hypoxia by an increase in the synthesis of HIF-1α and HSP₇₀. Course application of 1 % oromucosal gel with IL-1β receptor antagonist (1 μg/kg) to rats with CGP in a therapeutic regimen led to an improvement in the clinical picture of the disease: significant reduction in the size of the gingival pocket to 2.2 mm, and a significant reduction of bleeding and swelling against the background of lowering the levels of inflammatory markers in the blood: TNF-α – by 82 % (p < 0.05), metalloproteinase-2 – by 65 % (p < 0.05), and IL-1β – by 71.4 % (p < 0.05) compared to the group of untreated animals. Application of 1 % oromucosal gel with IL-1β receptor antagonist resulted in an increase in HIF-1α levels by 42 % (p < 0.05) in comparison to control indicators, and an increase in HSP₇₀ levels by 62.8 % compared to the control group, and in 2.4 times (p < 0.05) compared to the intact group that indicated a significant impact of IL-1β receptor antagonist on the HSP₇₀-dependent mechanisms of endogenous cytoprotection. Oromucosal gel with 1 % IL-1β receptor antagonist (1 μg/kg) was significantly superior to the reference drug Mexidol (250 mg/kg) in terms of its action on the studied parameters under conditions of CGP.

Conclusions. The obtained results substantiate the further in-depth pharmacological study of the new oromucosal gel with IL-1β receptor antagonist (1 μg/kg) for the purpose of clinical use in the treatment of generalized periodontitis. We have found that the use of IL-1β receptor antagonist in experimental CGP is more effective than Mexidol.