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

Document Type : Original Article

Authors

1 Department of Pharmacology, Faculty of Medicine, Tekirdag Namık Kemal University, Tekirdag, Turkey

2 Department of Pharmacology, Faculty of Medicine, Kafkas University, Kars, Turkey

3 Department of Pharmacology, Faculty of Medicine, Sutcu Imam University, Kahramanmaraş, Turkey

4 Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey

5 Clinical Research, Development and Design Application and Research Center, Ataturk University, Erzurum, Turkey

6 Department of Ophthalmology, University of Health Science, Ümraniye Education and Research Hospital, Department of Ophthalmology, Istanbul, Turkey

7 Department of Histology and Embryology, Faculty of Medicine, Kafkas University, Kars, Turkey

Abstract

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  μg/kg lipopolysaccharide (LPS), SC), DEX group (200  μg/kg LPS plus 1  mg/kg dexamethasone, IP), AGO20 group received 200 μg/kg LPS plus 20 mg/kg AGO, AGO40 group received 200  μg/kg LPS plus 40  mg/kg AGO, RAME2 group received 200 μg/kg LPS plus 2  mg/kg RAME, and group RAME4 received 200 μg/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-α (TNF-α), 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-α, 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.

Keywords

References

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Iranian Journal of Basic Medical Sciences
Volume 26, Issue 5
May 2023
Pages 540-548

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