title: Protective effects of melatonin and selenium against apoptosis of olfactory sensory neurons: A rat model study.
abstract: BACKGROUND
  Selenium plays a role in the prevention of oxidative damage and has been linked to regulatory functions in cell growth, apoptosis, cell survival, and cytotoxicity. Melatonin has an antioxidant effect, which protects against a number of free radical species. Given its antioxidant properties, melatonin has been widely known to inhibit neuronal apoptosis. We examined the cytoprotective effects of melatonin and selenium in rat olfactory sensory neurons after rhinosinusitis by immunohistochemical evaluation of olfactory bulb mucosa.
  
  
  METHODS
  Rhinosinusitis was induced bilaterally in 24 animals. Twenty-four rats were randomly divided into three equal groups. The melatonin group was treated with intraperitoneal (i.p.) melatonin and ampicillin-sulbactam, the selenium group was treated with i.p. selenium and ampicillin-sulbactam, the antibiotic group was treated with i.p. ampicillin-sulbactam; all three groups were treated for 10 days. After a period of 10 days of treatment, the animals were killed for immunohistochemical analyses. All olfactory bulb mucosae were removed immediately.
  
  
  RESULTS
  No histochemical differences were found in the three groups. Terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling-positive cells were detected in each group. In the antibiotic group, the appearance of apoptotic cells was higher, whereas the number of apoptotic cells significantly decreased in the melatonin group. When compared with the selenium group, fewer terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling-positive cells were observed in the melatonin group, which was not significant. In the antibiotic group, the cytoplasmic active caspase-3 and Bax immunostaining in the olfactory epithelium and glandular cells of stroma were higher when compared with the immunostaining in melatonin and selenium groups. Active caspase-3 and Bax immunostaining in the subepithelial stroma was dramatically reduced in the melatonin group. In contrast, the staining intensity and the number of Bcl-2 immunopositive cells were significantly increased in the melatonin group. In the selenium group, Bax and active caspase-3 were moderately immunopositive in the epithelium and subepithelial stroma. However, Bcl-2 immunostaining was more pronounced in the olfactory epithelium and some stromal cells.
  
  
  CONCLUSIONS
  Our results indicated the possibility that the supplementation of melatonin and selenium, two antioxidant agents for the treatments in the rhinosinusitis rat model, might be reduced or prevent anosmia.
authors.affiliation: Department of ENT Head and Neck Surgery, Antalya Education and Research Hospital, Antalya, Turkey.
authors.forename: Sema
authors.initials: S
authors.lastname: Koc
authors.forename: Sevil
authors.initials: S
authors.lastname: Cayli
authors.forename: Ceyhun
authors.initials: C
authors.lastname: Aksakal
authors.forename: Seda
authors.initials: S
authors.lastname: Ocakli
authors.forename: Harun
authors.initials: H
authors.lastname: Soyalic
authors.forename: Battal Tahsin
authors.initials: BT
authors.lastname: Somuk
authors.forename: Salim
authors.initials: S
authors.lastname: Yüce
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008550:Melatonin / Q000627:therapeutic use*; D023421:Models, Animal; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009830:Olfactory Bulb / Q000187:drug effects* / Q000473:pathology; D009831:Olfactory Mucosa / Q000187:drug effects* / Q000473:pathology; D018034:Olfactory Receptor Neurons / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D012220:Rhinitis / Q000188:drug therapy*; D012643:Selenium / Q000627:therapeutic use*; D012852:Sinusitis / Q000188:drug therapy*
chemical_list: D018696:Neuroprotective Agents; D053148:Caspase 3; D012643:Selenium; D008550:Melatonin