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Inflammation Research
Published in: Inflammation Research 5/2012

01-05-2012 | Original Research Paper

Histamine modulates salivary secretion and diminishes the progression of periodontal disease in rat experimental periodontitis

Authors: Juan P. Prestifilippo, Eliana Carabajal, Máximo Croci, Javier Fernández-Solari, Elena S. Rivera, Juan C. Elverdin, Vanina A. Medina

Published in: Inflammation Research | Issue 5/2012

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Abstract

Objective

We have recently reported that experimental periodontitis (EP) reduced methacholine-induced submandibular gland (SMG) salivary secretion. The aim of the present study was to determine whether histamine could prevent SMG impairment produced by EP.

Materials and Methods

Bilateral EP was induced for 2 weeks and histamine treatment (0.1 mg/kg subcutaneously) was started 5 days before the end of the experimental period in male rats. The histamine effects on periodontitis-altered functional and histological parameters of SMG and on periodontal bone loss were evaluated.

Results

Histamine treatment partially reversed the methacholine-induced salivation reduction produced by EP while preventing SMG histological damage. Histamine’s effect on SMG was associated with an increased proliferation rate (2.2 ± 0.3 vs. 0.2 ± 0.2 proliferative cells per field, P < 0.001). Furthermore, histamine completely prevented enhanced EP-induced apoptosis (1.0 ± 0.4 vs. 60.9 ± 4.6 apoptotic cells per field, P < 0.001). The protective effect exerted by histamine on SMG functionality is associated with attenuation of lingual and vestibular bone loss (0.66 ± 0.04 vs. 0.97 ± 0.06 mm; P < 0.001).

Conclusions

Histamine is able to reduce periodontitis-induced damage to SMG and bone structure.
Literature
1.
Zelles T, Purushotham KR, Macauley SP, Oxford GE, Humphreys-Beher MG. Saliva and growth factors: the fountain of youth resides in us all. J Dent Res. 1995;74:1826–32.PubMedCrossRef
2.
3.
Llena-Puy C. The role of saliva in maintaining oral health and as an aid to diagnosis. Med Oral Patol Oral Cir Bucal. 2006;11:449–55.
4.
Slomiany BL, Murty VL, Piotrowski J, Slomiany A. Salivary mucins in oral mucosal defense. Gen Pharmacol. 1996;27:761–71.PubMedCrossRef
5.
Slomiany A, Nishikawa H, Slomiany BL. Screening and modulation of extracellular signals by mucous barrier. Serum glycosylphosphatidylinositol phospholipase D (GPIPLD) releases protective mucous barrier from oral mucosa. J Physiol Pharmacol. 2002;53:21–38.PubMed
6.
Pedersen AM, Bardow A, Jensen SB, Nauntofte B. Saliva and gastrointestinal functions of taste, mastication, swallowing and digestion. Oral Dis. 2002;8:117–29.PubMedCrossRef
7.
8.
Page RC, Schroeder HE. Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest. 1976;34:235–49.PubMed
9.
Creamer HR. A novel hypothesis concerning the mechanisms of activation, and of control, of periodontal bone loss. Med Hypotheses. 1991;35:115–21.PubMedCrossRef
10.
Deo V, Bhongade ML. Pathogenesis of periodontitis: role of cytokines in host response. Dent Today. 2010;29:60–2.PubMed
11.
Hirotomi T, Yoshihara A, Ogawa H, Ito K, Igarashi A, Miyazaki H. A preliminary study on the relationship between stimulated saliva and periodontal conditions in community-dwelling elderly people. J Dent. 2006;34:692–8.PubMedCrossRef
12.
Hirotomi T, Yoshihara A, Ogawa H, Ito K, Igarashi A, Miyazaki H. Salivary spinability and periodontal disease progression in an elderly population. Arch Oral Biol. 2008;53:1071–6.PubMedCrossRef
13.
Dawes C. Factors influencing salivary flow rate and composition. In: Edgar WM, O’Mullane DM, editors. Saliva and Oral Health. 2nd ed. London: British Dental Association; 1996. p. 27–41.
14.
Tandler B, Phillips CJ. Microstructure of mammalian salivary glands and its relationship to diet. In: Garret JR, Ekstrom J, Anderson LC, (eds). Glandular Mechanisms of Salivary Secretion. Oral Frontiers on Biology; Karger, Basel, Switzerland: 1998. pp 21–35.
15.
Amer M, Elverdin JC, Fernández-Solari J, Medina VA, Chiarenza AP, Vacas MI. Reduced methacholine-induced submandibular salivary secretion in rats with experimental periodontitis. Arch Oral Biol. 2011;56:421–7.PubMedCrossRef
16.
Fernandez-Solari J, Prestifilippo JP, Ossola CA, Rettori V, Elverdin JC. Participation of the endocannabinoid system in lipopolysaccharide-induced inhibition of salivary secretion. Arch Oral Biol. 2010;55:583–90.PubMedCrossRef
17.
Fernandez-Solari J, Prestifilippo JP, Bornstein SR, McCann SM, Rettori V. Participation of the endocannabinoid system in the effect of TNF-alpha on hypothalamic release of gonadotropin-releasing hormone. Ann N Y Acad Sci. 2006;1088:238–50.PubMedCrossRef
18.
Ekuni D, Endo Y, Irie K, Azuma T, Tamaki N, Tomofuji T, Morita M. Imbalance of oxidative/anti-oxidative status induced by periodontitis is involved in apoptosis of rat submandibular glands. Arch Oral Biol. 2010;55:170–6.PubMedCrossRef
19.
20.
Al-Hashimi I. The management of Sjogren’s syndrome in dental practice. J Am Dent Assoc. 2001;132:1409–17.PubMed
21.
Valdez IH, Atkinson JC, Ship JA, Fox PC. Major salivary gland function in patients with radiation-induced xerostomia: Flow rates and sialochemistry. Int J Radiat Oncol Biol Phys. 1993;25:41–7.PubMedCrossRef
22.
Nagler RM. The enigmatic mechanism of irradiation-induced damage to the major salivary glands. Oral Dis. 2002;8:141–6.PubMedCrossRef
23.
Valdez IH, Atkinson JC, Ship JA, Fox PC. Major salivary gland function in patients with radiation-induced xerostomia: flow rates and sialochemistry. Int J Radiat Oncol Biol Phys. 1993;25:41–7.PubMedCrossRef
24.
Burlage FR, Coppes RP, Meertens H, Stokman MA, Vissink A. Parotid and submandibular/sublingual salivary flow during high dose radiotherapy. Radiother Oncol. 2001;31:271–3.CrossRef
25.
Burlage FR, Roesink JM, Kampinga HH, Coppes RP, Terhaard C, Langendijk JA, van Luijk P, Stokman MA, Vissink A. Protection of salivary function by concomitant pilocarpine during radiotherapy: a double-blind, randomized placebo-controlled study. Int J Radiat Oncol Biol Phys. 2008;70:14–22.PubMedCrossRef
26.
Medina VA, Prestifilippo JP, Croci M, Carabajal E, Bergoc RM, Elverdin JC, Rivera ES. Histamine prevents functional and morphological alterations of submandibular glands induced by ionising radiation. Int J Radiat Biol. 2011;87(3):284–92.PubMedCrossRef
27.
Dy M, Schneider E. Histamine-cytokine connection in immunity and hematopoiesis. Cytokine Growth Factor Rev. 2004;15:393–410.PubMedCrossRef
28.
Medina VA, Rivera ES. Histamine receptors and cancer pharmacology. Br J Pharmacol. 2010;161:755–67.PubMedCrossRef
29.
Stanovnik L, Erjavec F. The inhibition of salivary secretion by histamine H2-antagonists: a study on the cat submandibular gland. Agents Actions. 1983;13:196–9.PubMedCrossRef
30.
Shimizu T, Taira N. Pharmacological analysis of salivary and blood flow responses to histamine of the submandibular gland of the dog. Br J Pharmacol. 1980;68:651–61.PubMed
31.
Kim JH, Park SH, Moon YW, Hwang S, Kim D, Jo SH, Oh SB, Kim JS, Jahng JW, Lee JH, Lee SJ, Choi SY, Park K. Histamine H1 receptor induces cytosolic calcium increase and aquaporin translocation in human salivary gland cells. J Pharmacol Exp Ther. 2009;330:403–12.PubMedCrossRef
32.
Goya JA, Paez HA, Mandalunis PM. Effect of topical administration of monosodium olpadronate on experimental periodontitis in rats. J Periodontol. 2006;77:1–6.PubMedCrossRef
33.
Bianciotti LG, Elverdin JC, Vatta MS, Colatrella C, Fernández BE. Atrial natriuretic factor enhances induced salivary secretion in the rat. Regul Pept. 1994;49:195–202.PubMedCrossRef
34.
Crawford JM, Taubman MA, Smith DJ. The natural history of periodontal bone loss in germfree and gnotobiotic rats infected with periodontopathic microorganisms. J Periodontal Res. 1978;13:316–25.PubMedCrossRef
35.
36.
Kinney JS, Ramseier CA, Giannobile WV. Oral fluid-based biomarkers of alveolar bone loss in periodontitis. Ann N Y Acad Sci. 2007;1098:230–51.PubMedCrossRef
37.
Tobita M, Uysal AC, Ogawa R, Hyakusoku H, Mizuno H. Periodontal tissue regeneration with adipose-derived stem cells. Tissue Eng Part A. 2008;14:945–53.PubMedCrossRef
38.
Yamasaki A, Nikai H, Niitani K, Ijuhin N. Ultrastructure of the junctional epithelium of germfree rat gingiva. J Periodontol. 1979;50:641–8.PubMedCrossRef
39.
Peruzzo DC, Benatti BB, Antunes IB, Andersen ML, Sallum EA, Casati MZ, Nociti FH, Nogueira-Filho GR. Chronic stress may modulate periodontal disease: a study in rats. J Periodontol. 2008;79:697–704.PubMedCrossRef
40.
Goya JA, Paez HA, Mandalunis PM. Effect of topical administration of monosodium olpadronate on experimental periodontitis in rats. J Periodontol. 2006;77(1):1–6.PubMedCrossRef
41.
Page R, Schroeder H. Periodontitis in man and other animals: a comparative review. Karger; Basel: 1982.
42.
Muhvic-Urek M, Bralic M, Curic S, Pezelj-Ribaric S, Borcic J, Tomac J. Imbalance between apoptosis and proliferation causes late radiation damage of salivary gland in mouse. Physiol Res. 2006;55:89–95.PubMed
43.
Takagi K, Yamaguchi K, Sakurai T, Asari T, Hashimoto K, Terakawa S. Secretion of saliva in X-irradiated rat submandibular glands. Radiat Res. 2003;159:351–60.PubMedCrossRef
44.
Yoshida T, Iwakiri R, Noda T, Okamoto K, Kojima M, Fukuyama K, Fujimoto K. Histaminergic effect on apoptosis of rat small intestinal mucosa after ischemia–reperfusion. Dig Dis Sci. 2000;45:1138–44.PubMedCrossRef
45.
Fujimoto K, Iwakiri R, Yoshida T, Noda T, Kojima M, Utsumi H, Wu B, Okada K, Sakata Y, Ootani A. Histaminergic effect on apoptosis of small intestinal mucosa after ischemia–reperfusion in the rat. In: Watanabe T, Timmerman H, Yanai K, editors. Histamine research in the new millennium. Amsterdam: Elsevier; 2001. p. 185–90.
46.
Medina VA, Croci M, Mohamad NA, Massari N, Garbarino G, Cricco GP, Núñez MA, Martín GA, Crescenti EJ, Bergoc RM, Rivera ES. Mechanisms underlying the radioprotective effect of histamine on small intestine. Int J Radiat Biol. 2007;83:653–63.PubMedCrossRef
47.
Saeki K, Seo S, Murakami M, Ikehara I. Effect of histamine on cyclic AMP levels in the submandibular gland. Agents Actions. 1981;11:156–7.PubMedCrossRef
48.
Borda E, Stranieri G, Sterin-Borda L. H(1)-Receptor activation triggers the endogenous nitric oxide signalling system in the rat submandibular gland. Mediators Inflamm. 2002;11:337–43.PubMedCrossRef
49.
Sim MK, Ang SB. Specific 3H-cimetidine binding to receptors in the submandibular gland of the rat. Jpn J Pharmacol. 1985;37:203–6.PubMedCrossRef
50.
Elad S, Heisler S, Shalit M. Saliva secretion in patients with allergic rhinitis. Int Arch Allergy Immunol. 2006;141(3):276–80.PubMedCrossRef
51.
Nin T, Umemoto M, Negoro A, Miuchi S, Sakagami M. Nizatidine enhances salivary secretion in patients with dry mouth. Auris Nasus Larynx. 2008;35(2):224–9.PubMedCrossRef
52.
Hasturk H, Kantarci A, Ebrahimi N, Andry C, Holick M, Jones VL, Van Dyke TE. Topical H2 antagonist prevents periodontitis in a rabbit model. Infect Immun. 2006;74(4):2402–14.PubMedCrossRef
53.
Vacas MI, Amer M, Chiarenza AP, Luchelli MA, Mandalunis PM, Elverdin JC. Influence of submandibulectomy on alveolar bone loss in rats. J Periodontol. 2008;79(6):1075–80.PubMedCrossRef
54.
Kuhr A, Popa-Wagner A, Schmoll H, Schwahn C. Observations on experimental marginal periodontitis in rats. J Periodontal Res. 2004;39:101–6.PubMedCrossRef
55.
Keremi B, Lohinai Z, Komora P, Duhaj S, Borsi K, Jobbagy-Ovari G, Kallo K, Szekely AD, Fazekas A, Dobo-Nagy C, Sikiric P, Varga G. Antiinflammatory effect of BPC 157 on experimental periodontitis in rats. J Physiol Pharmacol. 2009;60(Suppl 7):115–22.PubMed
56.
Båge T, Kats A, Lopez BS, Morgan G, Nilsson G, Burt I, Korotkova M, Corbett L, Knox AJ, Pino L, Jakobsson PJ, Modéer T, Yucel-Lindberg T. Expression of prostaglandin E synthases in periodontitis immunolocalization and cellular regulation. Am J Pathol. 2011;178(4):1676–88.PubMedCrossRef
57.
Guan SM, Fu SM, He JJ, Zhang M. Prevotella intermedia induces prostaglandin E2 via multiple signaling pathways. J Dent Res. 2011;90(1):121–7.PubMedCrossRef
58.
Yang LP, Perry CM. Spotlight on histamine dihydrochloride in acute myeloid leukaemia. Drugs Aging. 2011;28:325–9.PubMedCrossRef
59.
Galmarini CM. Histamine dihydrochloride (subcutaneous) Maxim. Curr Opin Investig Drugs. 2004;5:1298–310.PubMed
Metadata
Title
Histamine modulates salivary secretion and diminishes the progression of periodontal disease in rat experimental periodontitis
Authors
Juan P. Prestifilippo
Eliana Carabajal
Máximo Croci
Javier Fernández-Solari
Elena S. Rivera
Juan C. Elverdin
Vanina A. Medina
Publication date
01-05-2012
Publisher
SP Birkhäuser Verlag Basel
Published in
Inflammation Research / Issue 5/2012
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-011-0432-4

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