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

被引:2
作者
Yuksel, Tugba Nurcan [1 ]
Yayla, Muhammed [2 ]
Kose, Duygu [3 ]
Halici, Zekai [4 ,5 ]
Bozkurt, Erdinc [6 ]
Toktay, Erdem [7 ]
机构
[1] Tekirdag Namik Kemal Univ, Fac Med, Dept Pharmacol, Tekirdag, Turkiye
[2] Kafkas Univ, Fac Med, Dept Pharmacol, Kars, Turkiye
[3] Sutcu Imam Univ, Fac Med, Dept Pharmacol, Kahramanmaras, Turkiye
[4] Ataturk Univ, Fac Med, Dept Pharmacol, Erzurum, Turkiye
[5] Ataturk Univ, Dev & Design Applicat & Res Ctr, Clin Res, Erzurum, Turkiye
[6] Univ Hlth Sci, Umraniye Educ & Res Hosp, Dept Ophthalmol, Istanbul, Turkiye
[7] Kafkas Univ, Fac Med, Dept Histol & Embryol, Kars, Turkiye
关键词
Lipopolysaccharides; Melatonin; Oxidative stress; Uveitis; Rats; ENDOTHELIAL GROWTH-FACTOR; INFLAMMATION; APOPTOSIS; MODEL; RAMELTEON; CANCER; ASSAY; RISK;
D O I
10.22038/IJBMS.2023.67297.14749
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:540 / 548
页数:9
相关论文
共 61 条
[1]   Decreased serum melatonin levels in rats with experimental autoimmune uveitis/pinealitis and in patients with uveitis [J].
Abe, T ;
Tamada, H ;
Koizumi, T ;
Nakajima, A ;
Satoh, N ;
Sakuragi, S .
OCULAR IMMUNOLOGY AND INFLAMMATION, 1996, 4 (04) :175-182
[2]   Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation [J].
Ahmad, Sheikh Fayaz ;
Ansari, Mushtaq Ahmad ;
Zoheir, Khairy M. A. ;
Bakheet, Saleh A. ;
Korashy, Hesham M. ;
Nadeem, Ahmed ;
Ashour, Abdelkader E. ;
Attia, Sabry M. .
IMMUNOBIOLOGY, 2015, 220 (07) :889-898
[3]   Effects of Aliskiren, an RAAS inhibitor, on a carrageenan-induced pleurisy model of rats [J].
Bayir, Yasin ;
Un, Harun ;
Cadirci, Elif ;
Akpinar, Erol ;
Diyarbakir, Busra ;
Calik, Ilknur ;
Halici, Zekai .
ANAIS DA ACADEMIA BRASILEIRA DE CIENCIAS, 2019, 91 (01)
[4]   Can the CRP/albumin Ratio be Used as a New Indicator of Activation in Patients with Uveitis? [J].
Bozkurt, Erdinc ;
Muhafiz, Ersin ;
Sengul, Dilek ;
Ucak, Turgay ;
Atum, Mahmut .
OCULAR IMMUNOLOGY AND INFLAMMATION, 2021, 29 (05) :1017-1022
[5]   Melatonin: Buffering the Immune System [J].
Carrillo-Vico, Antonio ;
Lardone, Patricia J. ;
Alvarez-Sanchez, Nuria ;
Rodriguez-Rodriguez, Ana ;
Guerrero, Juan M. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2013, 14 (04) :8638-8683
[6]  
Celinski K, 2014, J PHYSIOL PHARMACOL, V65, P75
[7]   Mechanisms Underlying Benzyl Alcohol Cytotoxicity (Triamcinolone Acetonide Preservative) in Human Retinal Pigment Epithelial Cells [J].
Chang, Yi-Sheng ;
Lin, Chiou-Feng ;
Wu, Chao-Liang ;
Kuo, Pao-Ying ;
Wu, Fong-Sen ;
Shieh, Chi-Chang ;
Gean, Po-Wu ;
Chen, Shur-Tzu ;
Chen, Muh-Shy ;
Wu, Wen-Chuan ;
Tai, Ming-Hong ;
Tseng, Sung-Huei .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2011, 52 (07) :4214-4222
[8]   Inhibitory Effects of Glucosamine on Endotoxin-Induced Uveitis in Lewis Rats [J].
Chang, Yun-Hsiang ;
Horng, Chi-Ting ;
Chen, Yi-Hao ;
Chen, Po-Liang ;
Chen, Ching-Long ;
Liang, Chang-Min ;
Chien, Ming-Wei ;
Chen, Jiann-Torng .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2008, 49 (12) :5441-5449
[9]   Inhibition of experimental autoimmune uveitis by intravitreal AAV-Equine-IL10 gene therapy [J].
Crabtree, Elizabeth ;
Uribe, Katy ;
Smith, Sara M. ;
Roberts, Darby ;
Salmon, Jacklyn H. ;
Bower, Jacquelyn J. ;
Song, Liujiang ;
Bastola, Prabhakar ;
Hirsch, Matthew L. ;
Gilger, Brian C. .
PLOS ONE, 2022, 17 (08)
[10]   Risk of Ocular Complications in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis [J].
Dick, Andrew D. ;
Tundia, Namita ;
Sorg, Rachael ;
Zhao, Chen ;
Chao, Jingdong ;
Joshi, Avani ;
Skup, Martha .
OPHTHALMOLOGY, 2016, 123 (03) :655-662