Application of antioxidant and iNOS modulation therapy in lipopolysaccharide periodontitis associated with atrophic gastritis
DOI:
https://doi.org/10.11603/2311-9624.2019.4.10883Keywords:
periodontitis, atrophic gastritis, lycopene, aminoguanidineAbstract
Epidemiological investigations provide evidence linking a high incidence of inflammatory diseases of the oral cavity in individuals with atrophic changes in the gastric mucosa. In the pathogenesis of periodontitis induced by gram-negative microflora endotoxin lipopolysaccharide, the activation of free radical oxidation reactions and the excessive production of nitric oxide play an important role. Therefore, the using of drugs that would be able to prevent oxidative and nitrooxidative stress can be considered pathogenetically reasonable in periodontitis on the background of gastritis.
The aim of the study – to determine the therapeutic efficacy of antioxidant lycopene and inducible NO synthase selective inhibitor aminoguanidine in generalized lipopolysaccharide periodontitis associated with chronic atrophic gastritis.
Materials and Methods. Rats-males which were divided into 5 groups were used for experiments: group 1 – control; 2 – rats with lipopolysaccharide periodontitis on the background of chronic atrophic gastritis; 3 and 4 – rats with periodontitis and gastritis, which were respectively administered orally with lycopene or intraperitoneally with aminoguanidine; 5 – rats with periodontitis and gastritis, which were injected with lycopene and aminoguanidine together. In the serum and periodontal tissue homogenate the level of TBA-active products, reduced glutathione, the total activity of NO synthase, the level of nitrates and nitrites (NOx), the content of free oxyproline, glycosaminoglycans, sialic acids, TNF-α, IL-1β, IL-4, IL-10 were measured.
Results and Discussion. The use of lycopene reduced the intensity of oxidative reactions by 1.3 and 1.5 times in serum and periodontium, respectively, and increased the content of reduced glutathione by 1.2 times in serum of animals with periodontitis and gastritis. The activity of NO synthase in the periodontium under the influence of aminoguanidine decreased by 1.7 times, and the level of NOx – by 1.2 and 1.3 times in serum and periodontium. Under the influence of an antioxidant, the level of free oxyproline in the serum of animals with combined pathology decreased by 1.4 times, glycosaminoglycans – by 1.3 times, sialic acids – by 34 %, and under the influence of iNOS inhibitor – respectively by 40. 23 and 37 %. When using lycopene, the concentration of TNF-α and IL-1β decreased by 1.4 and 1.5 times compared with untreated animals, and the levels of IL-4 and IL-10 increased by 1.7 and 1.9 times, respectively. Aminoguanidine also significantly improved cytokine imbalance in rats with periodontitis and gastritis. Correction of periodontitis associated with gastritis with a combination of antioxidant and iNOS inhibitor has in most cases proved to be more effective than their individual use.
Conclusions. The use of antioxidant lycopene and iNOS inhibitor aminoguanidine can be considered as an effective pathogenetically reasonable method of correction of periodontitis associated with atrophic gastritis.
References
Noack, B., & Fischer, S. (2012). Metabolic diseases and periodontitis. Dtsch. Med. Wochenschr, 137 (22), 1155-1157.
Manashchyk, N.V., Chornii, N.V., & Shmanko, V.V. (2011). Vzaiemozviazok patolohii parodonta ta patolohii shlunkovo-kyshkovoho traktu [Interrelation of periodontal pathology and pathology of gastrointestinal tract. Klinichna stomatolohiia – Clinical Dentistry, (1-2), 23-27 [in Ukrainian].
Bedeniuk, O.S., & Korda, M.M. (2016). Rol oksydatyvnoho i nitrooksydatyvnoho stresu v patohenezi heneralizovanoho parodontytu na foni khronichnoho hastrytu [The role of oxidative and nitrooxidative stress in the pathogenesis of generalized periodontitis on the background of chronic gastritis]. Medychna ta klinichna khimiia – Medical and Clinical Chemistry, 18 (4), 11-15 [in Ukrainian].
Bedeniuk, O.S., & Korda, M.M. (2018). Imunna reaktyvnist orhanizmu pry heneralizovanomu parodontyti na foni khronichnoho atrofichnoho hastrytu [Immune reactivity of the body in generalized periodontitis on the background of chronic atrophic gastritis]. Visnyk problem biolohii i medytsyny – Bulletin of Problems of Biology and Medicine, 2 (1), 85-88 in Ukrainian.
Shcherba, V.V., & Korda, M.M. (2012). Zastosuvannia inhibitora indutsybelnoi syntazy oksydu azotu N-(3-(aminometyl)benzyn)atsetamidynu pry lipopolisaharydnomu zapalenni tkanyn parodontu The use of an inhibitor of inducible nitric oxide synthase N- (3- (aminomethyl) benzyl) acetamidine in lipopolysaccharide inflammation of periodontal tissues]. Medychna khimiia – Medical Chemistry, 14 (3), 76-79 in Ukrainian.
Wang, L., Chen, S., & Chen, Z. (2006). Morphological and pathologic changes of experimental chronic atrophic gastritis (CAG) and the regulating mechanism of protein expression in rats. J. Zhejiang Univ. SCIENCE B, 7 (8), 634-640. DOI: https://doi.org/10.1631/jzus.2006.B0634
Moyseyeva, E.G. (2008). Metabolicheskiy gomeostaz i imunnaya reaktivnost organizma v dinamike vospaleniya v tkanyah parodonta (eksperimentalnoye isslyedovaniye) [Metabolic homeostasis and immune reactivity of the body in the dynamics of inflammation in periodontal tissues (experimental study)]. Doctor’s Extended abstract [in Russian].
Sahin, K., Cross, B., & Sahin, N. (2015). Lycopene in the prevention of renal cell cancer in the TSC2 mutant Eker rat model. Arch. Biochem. Biophys., 15 (572), 36-39. DOI: https://doi.org/10.1016/j.abb.2015.01.006
Fartushna, A.M. (2012). NO-zalezhni zminy okysliuvalnoho metabolizmu u tkanynakh yasen bilykh shchuriv za umov khronichnoi intoksykatsii nitratom natriiu NO- dependent changes in oxidative metabolism in the tissues of white rat rats under chronic intoxication with sodium nitrate]. Problemy ekolohii ta medytsyny – Ecological and Medical Problems, 3-4 (16), 48-51 [in Ukrainian].
Andreeva, L.I. (1988). Modifikatsiya metoda opredeleniya perekisey lipidov v teste s tiobarbiturovoy kislotoy [Modification of the method for determination of peroxide in test with thiobarbituric acid]. Laboratornoye delo – Laboratory Science, (11), 41-43 [in Russian].
Ellman, G.L. Tissue sulfhydryl groups. Arch. of Bioch. and Biophys., 82, 70-77. DOI: https://doi.org/10.1016/0003-9861(59)90090-6
Stuehr, D., Kwon, N.S., Nathan, C., & Griffiths, O. (1991). N-Hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine. J. Biol. Chem., 266, 6259-6263. DOI: https://doi.org/10.1016/S0021-9258(18)38112-2
Ridnour, L., Sim, J.E., & Hayward, M. (2000). A spectrophotometric method for the direct detection and quantitation of nitric oxide, nitrite, and nitrate in cell culture media. Anal. Biochem., 281, 223-229. DOI: https://doi.org/10.1006/abio.2000.4583
Tetyanets, S.S. (1985) Metod opredeleniya svobodnogo olsiprolina v syvorotke krovi [Method for determination of free olsiproline in blood serum]. Laboratornoye delo – Laboratory Science, (1), 61-62 in Russian.
Sharayev, P.N., Pishkov, V.N., & Solovyova, N.I. (1987). Metod opredeleniya glikozaminglikanov v biologicheskikh zhidkostyakh [Method for the determination of glycosaminoglycans in biological fluids]. Laboratornoye delo – Laboratory Science, (5), 330-332 [in Russian].
Kolb, V.G., & Kamishnikov, V.S. (1976). Klinicheskaya biokhimiya [Clinical biochemistry]. Minsk-Minsk [in Russian].
Gublyer, Ye.V. (1978). Vycheslitelnyye metody analiza i razpoznavaniya patologicheskikh protsessov [Computational methods for the analysis and recognition of pathological processes]. Moscow: Meditsina in [Russian].