title: Pharmacological targeting of histamine H4 receptor in periodontal disease.
abstract: OBJECTIVE
  The objective of this study was to investigate whether histamine H4 receptor (H4 R) antagonists could prevent experimental periodontitis (EP)-induced histological, functional and inflammatory alterations in submandibular gland (SMG), periodontal bone and gingiva.
  
  
  METHODS
  Bilateral EP was induced for 2 weeks in anaesthetized male rats. The effect of systemic and local administration of H4 R antagonists (JNJ7777120, JNJ10191584) on histopathology and functionality of SMG, bone loss and gingival inflammation was evaluated.
  
  
  RESULTS
  The subcutaneous administration of JNJ7777120 prevented periodontitis-induced SMG histological injury, reducing vacuolization and apoptosis and additionally reversed the increased prostaglandin E2 (PGE2) levels in SMG while it partially reversed the methacholine-induced salivation reduction produced by periodontitis. JNJ7777120 attenuated bone loss and the increased PGE2 levels and inflammatory infiltration in gingival tissue of rats with periodontitis. Finally, local administration of JNJ7777120 and JNJ10191584 was also beneficial for improving periodontal parameters.
  
  
  CONCLUSIONS
  H4 receptor antagonists are able to ameliorate periodontitis-induced injury on SMG, gingival tissue and bone structure, suggesting that pharmacological targeting of H4 R could be an attractive strategy to improve periodontal health.
authors.affiliation: Physiology Department, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: J P
authors.initials: JP
authors.lastname: Prestifilippo
authors.affiliation: Physiology Department, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.|National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina.
authors.forename: J
authors.initials: J
authors.lastname: Fernández-Solari
authors.affiliation: Laboratory of Radioisotopes, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.|Laboratory of Cellular and Molecular Biology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, CONICET, Pontifical Catholic University of Argentina (UCA), Buenos Aires, Argentina.
authors.forename: D J
authors.initials: DJ
authors.lastname: Martinel Lamas
authors.affiliation: Physiology Department, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: C E
authors.initials: CE
authors.lastname: Rios
authors.affiliation: Physiology Department, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.|National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina.
authors.forename: C
authors.initials: C
authors.lastname: Mohn
authors.affiliation: Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: J C
authors.initials: JC
authors.lastname: Perazzo
authors.affiliation: Laboratory of Radioisotopes, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: E S
authors.initials: ES
authors.lastname: Rivera
authors.affiliation: Physiology Department, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: J C
authors.initials: JC
authors.lastname: Elverdin
authors.affiliation: Laboratory of Radioisotopes, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.|Laboratory of Cellular and Molecular Biology, Institute for Biomedical Research (BIOMED), School of Medical Sciences, CONICET, Pontifical Catholic University of Argentina (UCA), Buenos Aires, Argentina.
authors.forename: V A
authors.initials: VA
authors.lastname: Medina
mesh_terms: D016301:Alveolar Bone Loss / Q000188:drug therapy / Q000473:pathology; D000539:Alveolar Process / Q000187:drug effects / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D005881:Gingiva / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D006633:Histamine Antagonists / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D058990:Molecular Targeted Therapy; D010510:Periodontal Diseases / Q000473:pathology / Q000517:prevention & control*; D010518:Periodontitis / Q000188:drug therapy / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D013363:Submandibular Gland / Q000187:drug effects / Q000473:pathology
chemical_list: D006633:Histamine Antagonists; C498828:Hrh4 protein, rat; D007211:Indoles; D010879:Piperazines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D016210:Methacholine Chloride; C484309:1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine
keywords: JNJ7777120; apoptosis; gingivitis; inflammation; periodontitis; submandibular gland