Mohsen Chamanara1, Amir Rashidian1,2, Shahram Ejtemaei Mehr1, Ahmad-Reza Dehpour1,2, Reza Shirkohi3, Reyhaneh Akbarian1, Alireza Abdollahi4, Seyed-Mahdi Rezayat5. 1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. 2. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. 3. Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran. 4. Department of Pathology, Imam Hospital, Tehran University of Medical Sciences, Tehran, Iran. 5. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. Rezayat@tums.ac.ir.
Abstract
AIM: The aim of the present study is to investigate the anti-inflammatory effect of melatonin in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis through the inhibition of Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signalling pathway and activation of melatonin receptor. METHODS: Colitis was induced in Wistar rats by administration of 100 mg/kg TNBS dissolved in 0.25 ml of 50% ethanol solution using a flexible plastic rubber catheter into the colon via the anus. This resulted in incidence of colitis on the first day, and all treatments were conducted for 10 days after induction of colitis. Melatonin was administered intraperitoneally (i.p.) at doses of 1, 5, and 10 mg/kg/day. Luzindole (non-selective MT1/MT2 receptor antagonist) was administered i.p. at dose of 5 mg/kg/day 15 min prior to melatonin injection. During the experiment, animals were monitored for the appearance of diarrhoea, body weight loss, and rectal bleeding. Myeloid peroxidase enzyme and tumour necrosis factor-α (TNF-α) activities were detected by immunohistochemistry. The protein expression level of TLR4, myeloid differentiation factor 88 (MyD88), NF-κB p65, and inhibitor of kappa B (I-κB) were detected by western blotting analysis. RESULTS: Treatment with melatonin improved weight loss, mucosal, and histological damage compared with TNBS group. In addition, melatonin decreased TNBS-induced up-regulation of TLR4, MyD88, and NF-κB p65, and increased down-regulation of I-κB proteins. On the other hand, the administration of luzindole resulted in the inhibition of melatonin effects. CONCLUSIONS: It seems that the inhibition of TLR4/NF-κB signalling pathway may mediate the anti-inflammatory effects of melatonin in TNBS-induced rat colitis.
AIM: The aim of the present study is to investigate the anti-inflammatory effect of melatonin in trinitrobenzene sulfonic acid (TNBS)-induced ratcolitis through the inhibition of Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signalling pathway and activation of melatonin receptor. METHODS:Colitis was induced in Wistar rats by administration of 100 mg/kg TNBS dissolved in 0.25 ml of 50% ethanol solution using a flexible plastic rubber catheter into the colon via the anus. This resulted in incidence of colitis on the first day, and all treatments were conducted for 10 days after induction of colitis. Melatonin was administered intraperitoneally (i.p.) at doses of 1, 5, and 10 mg/kg/day. Luzindole (non-selective MT1/MT2 receptor antagonist) was administered i.p. at dose of 5 mg/kg/day 15 min prior to melatonin injection. During the experiment, animals were monitored for the appearance of diarrhoea, body weight loss, and rectal bleeding. Myeloid peroxidase enzyme and tumour necrosis factor-α (TNF-α) activities were detected by immunohistochemistry. The protein expression level of TLR4, myeloid differentiation factor 88 (MyD88), NF-κB p65, and inhibitor of kappa B (I-κB) were detected by western blotting analysis. RESULTS: Treatment with melatonin improved weight loss, mucosal, and histological damage compared with TNBS group. In addition, melatonin decreased TNBS-induced up-regulation of TLR4, MyD88, and NF-κB p65, and increased down-regulation of I-κB proteins. On the other hand, the administration of luzindole resulted in the inhibition of melatonin effects. CONCLUSIONS: It seems that the inhibition of TLR4/NF-κB signalling pathway may mediate the anti-inflammatory effects of melatonin in TNBS-induced ratcolitis.
Authors: David Dahlgren; Maria-José Cano-Cebrián; Per M Hellström; Alkwin Wanders; Markus Sjöblom; Hans Lennernäs Journal: Int J Mol Sci Date: 2020-09-15 Impact factor: 5.923