title: The effects of heparan sulphate mimetic RGTA-OTR4120 on irradiated murine salivary glands.
abstract: BACKGROUND
  This study focuses on the potential of ReGeneraTing Agent OTR4120 (RGTA-OTR4120) to treat radiation-induced damage of salivary glands. RGTAs are biopolymers designed to mimic the effects of heparan sulphate, thereby stimulation tissue repair and regeneration.
  
  
  METHODS
  C3H mice were irradiated with a single dose of 15 Gy in the head and neck region. RGTA-OTR4120 was injected 24 h after radiotherapy, followed by weekly injections. At 2, 6 and 10 weeks after radiotherapy, salivary flow rates were measured and animals were sacrificed to obtain parotid and submandibular glands for histology. Periodic acid Schiff stain was performed to visualize mucins that are produced by acinar cells. Amylase and total protein content were measured in saliva samples.
  
  
  RESULTS
  Salivary flow rates were increased at 2 weeks, but not at 6 and 10 weeks after radiotherapy with RGTA-OTR4120 administration, compared to irradiated controls. Two and 10 weeks after radiotherapy, the mucin production activity of acinar cells was increased under influence of RGTA administration. RGTA-OTR4120 did not influence amylase or total protein secretion.
  
  
  CONCLUSIONS
  RGTA-OTR4120 administration has a positive effect on salivary flow rates in irradiated mice on the short term. The effect was absent 10 weeks after radiotherapy, while at that time point, mucin producing activity of acinar cells was elevated by RGTA-OTR4120 administration. Given these results and the advantages of RGTA use in irradiated patients, further investigation on the potential of this drug to treat radiation-induced salivary gland damage, alone or in combination with other drugs, such as amifostine, is suggested.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Erasmus MC, 3000 CA Rotterdam, The Netherlands. l.spiegelberg@erasmusmc.nl
authors.forename: Linda
authors.initials: L
authors.lastname: Spiegelberg
authors.forename: Urville M
authors.initials: UM
authors.lastname: Djasim
authors.forename: Johan W
authors.initials: JW
authors.lastname: van Neck
authors.forename: Eppo B
authors.initials: EB
authors.lastname: Wolvius
authors.forename: Karel G H
authors.initials: KG
authors.lastname: van der Wal
mesh_terms: D061354:Acinar Cells / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D000681:Amylases / Q000032:analysis; D000818:Animals; D040761:Biomimetic Materials / Q000627:therapeutic use*; D005260:Female; D006025:Glycosaminoglycans / Q000627:therapeutic use*; D006497:Heparan Sulfate; D007267:Injections; D051379:Mice; D008809:Mice, Inbred C3H; D009077:Mucins / Q000032:analysis; D010306:Parotid Gland / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000188:drug therapy*; D011897:Random Allocation; D012463:Saliva / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D012469:Salivary Glands / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D012471:Salivary Proteins and Peptides / Q000032:analysis; D012636:Secretory Rate / Q000187:drug effects / Q000528:radiation effects; D013363:Submandibular Gland / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D013997:Time Factors
chemical_list: D000681:Amylases; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D009077:Mucins; D012471:Salivary Proteins and Peptides; C533322:OTR4120