Characteristics of HIF-1α and HSP70 MRNA Expression, Level, and Interleukins in Experimental Chronic Generalized Periodontitis

Objectives: Periodontal diseases are a rather complex problem of modern dentistry and do not have only medical but also social significance. The objective of this study is to weigh the effect of a mixture of Thiotriazoline and L-arginine (1:4) on the parameters of the system of endogenous cytoprotection of blood and periodontal illness in rats with experimental chronic generalized periodontitis and substantiate further study of this blend. Materials and Methods: The study aimed to evaluate the impact of a combination of Thiotriazoline and L-arginine (in a ratio of 1:4) on the parameters of the endogenous blood cytoprotection system and periodontium in rats with experimental chronic generalized periodontitis. A group of outbred rats weighing 190-220 g and sourced from the vivarium of the Institute of Pharmacology and Toxicology of the Academy of Medical Sciences of Ukraine were divided into four groups, each consisting of 10 animals. (1) Intact group, animals that were injected intragastrically with a solution of sodium chloride to chloride 0.9% for 30 days. (2) control, animals with experimental CGP who intragastrically sodium chloride solution 0.9% for 30 days. (3) animals with experimental CGP were injected intramuscularly with Thiotriazoline + L-arginine (1:4) in a dosage of 200 mg/kg (30 days). (4) animals with experimental CGP, for which daily intragastric reference drug Mexidol, in dosage 250 mg/kg (30 days). In this study, we utilized two substances: Thiotriazoline and L-arginine hydrochloride. The combination of Thiotriazoline and L-arginine (in a ratio of 1:4) was prepared at the Department of Pharmaceutical Chemistry of ZSMU. At the conclusion of the experiment, the rats were carefully removed from the study while under thiopental-sodium anesthesia, and administered at a dosage of 40 mg/kg. Results: We have found that the administration of a combined preparation of Thiotriazoline with L-arginine to rats with CGP leads to a significant decrease in the blood concentration of pro-inflammatory cytokines IL-1b and TNF-a by 56.1% and 71%, respectively. Conclusion: The administration of Mexidol at a dosage of 250 mg/kg, as well as the combination of Thiotriazoline and Larginine in a ratio of 1:4 at a dosage of 200 mg/kg, resulted in a significant reduction in gingival pocket depth in animals with CGP. Specifically, the gingival pocket depth was reduced to 6 mm (p < 0.05) with Mexidol and further reduced to 4 mm (p < 0.05) with the combination of Thiotriazoline and L-arginine. Additionally, the animals exhibited minimal bleeding, swelling, and tooth mobility when treated with the combination of Thiotriazoline and L-arginine. The administration of a combination of Thiotriazoline and L-arginine (in a ratio of 1:4) at a dosage of 200 mg/kg to animals with CGP resulted in a noteworthy reduction in the blood concentration of pro-inflammatory cytokines IL-1b and TNF-a. Specifically, there was a significant decrease of 56.1% (p < 0.05) in IL-1b and 71% (p < 0.05) in TNF-a levels. The course administration of a combination of Thiotriazoline and L-arginine (1:4) (200 mg/kg) to animals with CGP led to an increased expression of HSP70 mRNA (p < 0.05) in the periodontium by 8.2 times and HIF-1a mRNA by 8.2 times. 2.8 times (p < 0.05) against the background of an increase in the blood concentration of HSP70 by 95% (p < 0.05). Also, in the periodontium of animals in this group, a decrease in the expression of c-Fos mRNA by 36.7% (p < 0.05) was found compared to the control group.