Protective effects of melatonin receptor agonists on endotoxin- induced uveitis in rats


Yuksel T. N., YAYLA M., Kose D., HALICI Z., Bozkurt E., TOKTAY E.

IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, cilt.26, sa.5, ss.540-548, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 26 Sayı: 5
  • Basım Tarihi: 2023
  • Doi Numarası: 10.22038/ijbms.2023.67297.14749
  • Dergi Adı: IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, Index Islamicus, Veterinary Science Database, Directory of Open Access Journals
  • Sayfa Sayıları: ss.540-548
  • Anahtar Kelimeler: Lipopolysaccharides, Melatonin, Oxidative stress, Uveitis, Rats, ENDOTHELIAL GROWTH-FACTOR, INFLAMMATION, APOPTOSIS, MODEL, RAMELTEON, CANCER, ASSAY, RISK
  • Atatürk Üniversitesi Adresli: Evet

Özet

Objective(s): Melatonin has an important role in regulating a variety of physiological functions of the body. We investigated the protective effects of Agomelatine (AGO) and Ramelteon (RAME) on Endotoxin-Induced Uveitis (EIU) in rats. Materials and Methods: 70 rats were randomly divided into fourteen groups. Healthy group normal saline, (IP), Uveitis group (200 pg/kg lipopolysaccharide (LPS), SC), DEX group (200 pg/kg LPS plus 1 mg/kg dexamethasone, IP), AGO20 group received 200 pg/kg LPS plus 20 mg/kg AGO, AGO40 group received 200 pg/kg LPS plus 40 mg/kg AGO, RAME2 group received 200 pg/kg LPS plus 2 mg/kg RAME, and group RAME4 received 200 pg/kg LPS plus 4 mg/kg RAME. Each group had two subgroups: the 3rd and 24th hour. The eye tissues were collected and investigated biomicroscopically (clinical manifestations and scoring, molecularly(qRT-PCR analyses of Tumor Necrosis Factor-alpha (TNF-alpha), vascular endothelial growth factor(VEGF), and Caspase 3 and Caspase 9 mRNA expression), biochemically (Superoxide dismutase activity, Glutathione, and Malondialdehyde levels) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Results: Melatonin receptor agonist treatment reduced the clinical score count of ocular inflammation in the uveitic rats. TNF-alpha, VEGF, Caspase 9, and Caspase 3 levels markedly decreased in the uveitic rats. Melatonin receptor agonists significantly ameliorated fixed changes in GSH, SOD, and MDA levels. Melatonin receptor agonists also ameliorated histopathological injury in eye tissues associated with uveitis. Conclusion: Melatonin receptor agonists ameliorated the inflammatory response in EIU. These findings suggest that melatonin receptor agonists may represent a potential novel therapeutic drug for uveitis treatment.