The effect of luteolin in prevention of periodontal disease in Wistar rats.
luteolin
osteoblasts
osteoclasts
periodontitis
Journal
Journal of periodontology
ISSN: 1943-3670
Titre abrégé: J Periodontol
Pays: United States
ID NLM: 8000345
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
02
10
2018
revised:
08
05
2019
accepted:
11
05
2019
pubmed:
23
5
2019
medline:
9
4
2020
entrez:
23
5
2019
Statut:
ppublish
Résumé
Periodontal disease is the chronic infectious disease of the periodontium. Because of irreversibility, prevention of disease is one of the most important goals of periodontal treatment. The aim of this study was to evaluate the effect of luteolin, a powerful anti-inflammatory agent, on the prevention of experimental periodontitis by determining morphological and histological tissue alterations. This study consisted of 28 rats and four experimental groups: healthy control group (C, n = 6); periodontitis group (P, n = 6); periodontitis and 50 mg/kg luteolin administered group (L-50, n = 8); and periodontitis and 100 mg/kg luteolin administered group (L-100, n = 8). Experimental periodontitis was induced via ligature method around lower right first molar teeth. All rats were euthanized 11 days after. The severity of periodontal destruction was determined by measuring alveolar bone loss under a stereomicroscope. Osteoblast and inflammatory cell counts were counted on hematoxylin-eosin-stained slides and osteoclasts were counted on tartrate-resistant acid phosphatase-stained slides. The levels of inducible nitric oxide synthase (iNOS), bone morphogenetic protein (BMP)-2, matrix metalloproteinase (MMP)-8, tissue inhibitor of MMP (TIMP)-1, receptor activator of nuclear factor κB ligand (RANKL), and osteoprotegerin (OPG) were determined by immunohistochemistry. The highest alveolar bone loss was observed in the periodontitis group and the luteolin administration decreased bone loss in both groups. Osteoblast cell number was higher and osteoclast and inflammatory cell numbers were lower in the P group compared to C, L-50, and L-100 groups. Luteolin, dose-dependently increased osteoblast cell counts. Luteolin attenuated periodontal inflammation in both L-50 and L-100 groups. Like osteoblast cell numbers, BMP-2 expressions were also elevated in luteolin groups. Both doses of luteolin significantly increased TIMP-1 and BMP-2 expressions and decreased MMP-8 levels. iNOS expressions increased in P group and L-100 significantly decreased iNOS levels. RANKL increased and OPG decreased in P group and 100 mg/kg luteolin increased OPG and decreased RANKL levels significantly. Within the limits of present experimental study, luteolin successfully improved periodontal health in a ligature-induced experimental periodontitis model in Wistar rats. The decrease in inflammation, osteoclastic and collagenase activity and increase in osteoblastic activity are possibly involved in this process.
Sections du résumé
BACKGROUND
Periodontal disease is the chronic infectious disease of the periodontium. Because of irreversibility, prevention of disease is one of the most important goals of periodontal treatment. The aim of this study was to evaluate the effect of luteolin, a powerful anti-inflammatory agent, on the prevention of experimental periodontitis by determining morphological and histological tissue alterations.
METHODS
This study consisted of 28 rats and four experimental groups: healthy control group (C, n = 6); periodontitis group (P, n = 6); periodontitis and 50 mg/kg luteolin administered group (L-50, n = 8); and periodontitis and 100 mg/kg luteolin administered group (L-100, n = 8). Experimental periodontitis was induced via ligature method around lower right first molar teeth. All rats were euthanized 11 days after. The severity of periodontal destruction was determined by measuring alveolar bone loss under a stereomicroscope. Osteoblast and inflammatory cell counts were counted on hematoxylin-eosin-stained slides and osteoclasts were counted on tartrate-resistant acid phosphatase-stained slides. The levels of inducible nitric oxide synthase (iNOS), bone morphogenetic protein (BMP)-2, matrix metalloproteinase (MMP)-8, tissue inhibitor of MMP (TIMP)-1, receptor activator of nuclear factor κB ligand (RANKL), and osteoprotegerin (OPG) were determined by immunohistochemistry.
RESULTS
The highest alveolar bone loss was observed in the periodontitis group and the luteolin administration decreased bone loss in both groups. Osteoblast cell number was higher and osteoclast and inflammatory cell numbers were lower in the P group compared to C, L-50, and L-100 groups. Luteolin, dose-dependently increased osteoblast cell counts. Luteolin attenuated periodontal inflammation in both L-50 and L-100 groups. Like osteoblast cell numbers, BMP-2 expressions were also elevated in luteolin groups. Both doses of luteolin significantly increased TIMP-1 and BMP-2 expressions and decreased MMP-8 levels. iNOS expressions increased in P group and L-100 significantly decreased iNOS levels. RANKL increased and OPG decreased in P group and 100 mg/kg luteolin increased OPG and decreased RANKL levels significantly.
CONCLUSIONS
Within the limits of present experimental study, luteolin successfully improved periodontal health in a ligature-induced experimental periodontitis model in Wistar rats. The decrease in inflammation, osteoclastic and collagenase activity and increase in osteoblastic activity are possibly involved in this process.
Identifiants
pubmed: 31115905
doi: 10.1002/JPER.18-0584
doi:
Substances chimiques
Osteoprotegerin
0
RANK Ligand
0
Luteolin
KUX1ZNC9J2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1481-1489Informations de copyright
© 2019 American Academy of Periodontology.
Références
Knight ET, Liu J, Seymour GJ, Faggion CM Jr., Cullinan MP. Risk factors that may modify the innate and adaptive immune responses in periodontal diseases. Periodontol 2000. 2016;71:22-51.
Reynolds MA. Modifiable risk factors in periodontitis: at the intersection of aging and disease. Periodontol 2000. 2014;64:7-19.
D'aiuto F, Nibali L, Parkar M, Patel K, Suvan J, Donos N. Oxidative stress, systemic inflammation, and severe periodontitis. J Dent Res. 2010;89:1241-1246.
Huh Y, Kim J, Kim H, et al. Regulation of osteoclast differentiation by the redox-dependent modulation of nuclear import of transcription factors. Cell Death Differ. 2006;13:1138.
Baek KH, Oh KW, Lee WY, et al. Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures. Calcif Tissue Int. 2010;87:226-235.
Domazetovic V, Marcucci G, Iantomasi T, Brandi ML, Vincenzini MT. Oxidative stress in bone remodeling: role of antioxidants. Clin Cases Miner Bone Metab. 2017;14:209-216.
Lee D, Lim B-S, Lee Y-K, Yang H-C. Effects of hydrogen peroxide (H2O2) on alkaline phosphatase activity and matrix mineralization of odontoblast and osteoblast cell lines. Cell Biol Toxicol. 2006;22:39-46.
Bai X-c, Lu D, Bai J, et al. Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-κB. Biochem Biophys Res Commun. 2004;314:197-207.
Romagnoli C, Marcucci G, Favilli F, et al. Role of GSH/GSSG redox couple in osteogenic activity and osteoclastogenic markers of human osteoblast-like SaOS-2 cells. FEBS J. 2013;280:867-879.
Bonewald LF, Johnson ML. Osteocytes, mechanosensing and Wnt signaling. Bone. 2008;42:606-615.
Henriksen K, Neutzsky-Wulff AV, Bonewald LF, Karsdal MA. Local communication on and within bone controls bone remodeling. Bone. 2009;44:1026-1033.
Banfi G, Iorio EL, Corsi MM. Oxidative stress, free radicals and bone remodeling. Clin Chem Lab Med. 2008;46:1550-1555.
Cao JJ, Picklo MJ. N-acetylcysteine supplementation decreases osteoclast differentiation and increases bone mass in mice fed a high-fat diet. J Nutr. 2013;144:289-296.
Lee DE, Kim JH, Choi SH, Cha JH, Bak EJ, Yoo YJ. Periodontitis mainly increases osteoclast formation via enhancing the differentiation of quiescent osteoclast precursors into osteoclasts. J Per Res. 2015;50:256-264.
Kim T-H, Jung JW, Ha BG, et al. The effects of luteolin on osteoclast differentiation, function in vitro and ovariectomy-induced bone loss. J Nutr Biochem. 2011;22:8-15.
Hienz SA, Paliwal S, Ivanovski S. Mechanisms of bone resorption in periodontitis. J Immunol Res. 2015;2015:615486.
Chen Y, Dou C, Yi J, et al. Inhibitory effect of vanillin on RANKL-induced osteoclast formation and function through activating mitochondrial-dependent apoptosis signaling pathway. Life Sci. 2018;208:305-314.
Song F, Wei C, Zhou L, et al. Luteoloside prevents lipopolysaccharide-induced osteolysis and suppresses RANKL-induced osteoclastogenesis through attenuating RANKL signaling cascades. J Cell Physiol. 2018;233:1723-1735.
Crasto GJ, Kartner N, Yao Y, et al. Luteolin inhibition of V-ATPase a3-d2 interaction decreases osteoclast resorptive activity. J Cell Biochem. 2013;114:929-941.
Jia Z, Nallasamy P, Liu D, et al. Luteolin protects against vascular inflammation in mice and TNF-alpha-induced monocyte adhesion to endothelial cells via suppressing IΚBα/NF-κB signaling pathway. J Nutr Biochem. 2015;26:293-302.
Fei J, Liang B, Jiang C, Ni H, Wang L. Luteolin inhibits IL-1β-induced inflammation in rat chondrocytes and attenuates osteoarthritis progression in a rat model. Biomed Pharmacother. 2019;109:1586-1592.
Nash LA, Sullivan PJ, Peters SJ, Ward WE. Rooibos flavonoids, orientin and luteolin, stimulate mineralization in human osteoblasts through the Wnt pathway. Mol Nutr Food Res. 2015;59:443-453.
Jing Z, Wang C, Yang Q, et al. Luteolin attenuates glucocorticoid-induced osteoporosis by regulating ERK/Lrp-5/GSK-3β signaling pathway in vivo and in vitro. J Cell Physiol. 2018;234(4):4472-4490.
Gutiérrez-Venegas G, Contreras-Sánchez A. Luteolin and fisetin inhibit the effects of lipopolysaccharide obtained from Porphyromonas gingivalis in human gingival fibroblasts. Mol Biol Rep. 2013;40:477-485.
Gutiérrez-Venegas G, Bando-Campos CG. The flavonoids luteolin and quercetagetin inhibit lipoteichoic acid actions on H9c2 cardiomyocytes. Int Immunopharmacol. 2010;10:1003-1009.
Li M, Li Q, Zhao Q, Zhang J, Lin J. Luteolin improves the impaired nerve functions in diabetic neuropathy: behavioral and biochemical evidences. Int J Clin Exp Pathol. 2015;8:10112.
Chen Y, Sun X-B, Lu H-e, Wang F, Fan X-H. Effect of luteoin in delaying cataract in STZ-induced diabetic rats. Arch Pharm Res. 2017;40:88-95.
Toker H, Balci Yuce H, Lektemur Alpan A, Gevrek F, Elmastas M. Morphometric and histopathological evaluation of the effect of grape seed proanthocyanidin on alveolar bone loss in experimental diabetes and periodontitis. J Per Res. 2018;53:478-486.
Balci Yuce H, Karatas O, Aydemir Turkal H, et al. The effect of melatonin on bone loss, diabetic control, and apoptosis in rats with diabetes with ligature-induced periodontitis. J Periodontol. 2016;87:e35-e43.
Balci Yuce H, Lektemur Alpan A, Gevrek F, Toker H. Investigation of the effect of astaxanthin on alveolar bone loss in experimental periodontitis. J Per Res. 2018;53:131-138.
Prideaux M, Findlay DM, Atkins GJ. Osteocytes: the master cells in bone remodelling. Curr Opin Pharmacol. 2016;28:24-30.
Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423:337-342.
An J, Hao D, Zhang Q, et al. Natural products for treatment of bone erosive diseases: the effects and mechanisms on inhibiting osteoclastogenesis and bone resorption. Int Immunopharmacol. 2016;36:118-131.
Dar HY, Azam Z, Anupam R, Mondal RK, Srivastava RK. Osteoimmunology: the Nexus between bone and immune system. Front Biosci. 2018;23:464-492.
Xia F, Wang C, Jin Y, et al. Luteolin protects HUVECs from TNF-α-induced oxidative stress and inflammation via its effects on the Nox4/ROS-NF-κB and MAPK pathways. J Atheroscler Thromb. 2014;21:768-783.
Zhang X, Du Q, Yang Y, et al. The protective effect of Luteolin on myocardial ischemia/reperfusion (I/R) injury through TLR4/NF-κB/NLRP3 inflammasome pathway. Biomed Pharmacother. 2017;91:1042-1052.
Gutiérrez-Venegas G, Luna OA, Arreguín-Cano JA, Hernández-Bermúdez C. Myricetin blocks lipoteichoic acid-induced COX-2 expression in human gingival fibroblasts. Cell Mol Biol Lett. 2014;19:126.
Ammar N, El-Hawary S, Mohamed D, et al. Estrogenic activity including bone enhancement and effect on lipid profile of luteolin-7-O-glucoside isolated from Trifolium alexandrinum L. in ovariectomized rats. Phytother Res. 2016;30:768-773.
Yang H, Liu Q, Ahn JH, et al. Luteolin downregulates IL-1β-induced MMP-9 and-13 expressions in osteoblasts via inhibition of ERK signalling pathway. J Enzyme Inhib Med Chem. 2012;27:261-266.
Holzhausen M, Rossa C Jr., Marcantonio E Jr., Nassar PO, Spolidório DM, Spolidório LC. Effect of selective cyclooxygenase-2 inhibition on the development of ligature-induced periodontitis in rats. J Periodontol. 2002;73:1030-1036.
Graves DT, Kang J, Andriankaja O, Wada K, Rossa C Jr.. Animal models to study host-bacteria interactions involved in periodontitis. In: Periodontal Disease. vol. 15: Basel, Switzerland: Karger Publishers; 2012:117-132.
Oz HS, Puleo DA. Animal models for periodontal disease. BioMed Res Int. 2011;2011:754857.
Klausen B. Microbiological and immunological aspects of experimental periodontal disease in rats: a review article. J Periodontol. 1991;62:59-73.