title: Histopathologic changes in the middle ear mucosa after exposure to pepsin and unconjugated bile acid.
abstract: OBJECTIVE
  An increasing number of studies indicate that pepsin and bile acid cause damage to the ear, nose, and throat structures as a result of extraesophageal reflux. The aim of this study was to evaluate and compare the damaging effect of bile acids and pepsin on the middle ear mucosa.
  
  
  METHODS
  Twenty-nine healthy rats were included in this study. The animals were divided into 5 groups. A single daily dose of 40 μmol/L chenodeoxycholic acid, 40 μg/mL pepsin, and saline were injected separately into the right middle ear of the rats. On day 30, all rats were decapitated, and formalin-fixed, paraffin-embedded samples of the middle ear both from the control and experimental rats were prepared. A semiquantitative analysis was performed.
  
  
  RESULTS
  Inflammatory response was seen in all middle ear mucosa of rats except control group 1. The degree of inflammatory response was higher in the bile acid group when compared with the other groups. Epithelial metaplastic changes with varying number of goblet cells were observed in both the bile acid- and pepsin-injected groups. These metaplastic changes were also higher in the bile acid-induced group than in the pepsin-injected group.
  
  
  CONCLUSIONS
  This is the first study on the middle ear mucosal damage of both pepsin and bile acid. Our results demonstrate that bile acids were associated with more extensive mucosal injury at pH 7 in comparison to pepsin in a rat animal model. Inflammatory response and metaplastic changes may play an important role in the etiology of middle ear pathologies.
authors.affiliation: From the *Ear Nose Throat Head and Neck Surgery, Taksim Training and Research Hospital, Istanbul; †Trakya University, Vocational School of Health Services, Edirne; and ‡Department of Pathology, Taksim Training and Research Hospital; and Departments of §Pathology and ∥Medical Biochemistry, Istanbul University, Cerrahpaşa Medical Faculty, Istanbul.
authors.forename: Omer Necati
authors.initials: ON
authors.lastname: Develoglu
authors.forename: Enis
authors.initials: E
authors.lastname: Yalcin
authors.forename: Erdoğan
authors.initials: E
authors.lastname: Bulut
authors.forename: Saban
authors.initials: S
authors.lastname: Celebi
authors.forename: Elife
authors.initials: E
authors.lastname: Sahan
authors.forename: Nil
authors.initials: N
authors.lastname: Ustundag
authors.forename: Sergulen
authors.initials: S
authors.lastname: Dervisoglu
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kulekci
authors.forename: Mine
authors.initials: M
authors.lastname: Kucur
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000633:toxicity*; D004195:Disease Models, Animal; D004432:Ear, Middle / Q000187:drug effects* / Q000473:pathology*; D005764:Gastroesophageal Reflux / Q000150:complications* / Q000473:pathology*; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects* / Q000473:pathology; D010434:Pepsin A / Q000633:toxicity*; D051381:Rats
chemical_list: D001647:Bile Acids and Salts; D010434:Pepsin A