PMID- 30143913 OWN - NLM STAT- MEDLINE DCOM- 20190826 LR - 20200225 IS - 1568-5608 (Electronic) IS - 0925-4692 (Linking) VI - 27 IP - 2 DP - 2019 Apr TI - Melatonin ameliorates TNBS-induced colitis in rats through the melatonin receptors: involvement of TLR4/MyD88/NF-kappaB signalling pathway. PG - 361-371 LID - 10.1007/s10787-018-0523-8 [doi] AB - 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-kappaB) 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-alpha (TNF-alpha) activities were detected by immunohistochemistry. The protein expression level of TLR4, myeloid differentiation factor 88 (MyD88), NF-kappaB p65, and inhibitor of kappa B (I-kappaB) 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-kappaB p65, and increased down-regulation of I-kappaB 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-kappaB signalling pathway may mediate the anti-inflammatory effects of melatonin in TNBS-induced rat colitis. FAU - Chamanara, Mohsen AU - Chamanara M AD - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. FAU - Rashidian, Amir AU - Rashidian A AD - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. AD - Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. FAU - Mehr, Shahram Ejtemaei AU - Mehr SE AD - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. FAU - Dehpour, Ahmad-Reza AU - Dehpour AR AD - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. AD - Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. FAU - Shirkohi, Reza AU - Shirkohi R AD - Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran. FAU - Akbarian, Reyhaneh AU - Akbarian R AD - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. FAU - Abdollahi, Alireza AU - Abdollahi A AD - Department of Pathology, Imam Hospital, Tehran University of Medical Sciences, Tehran, Iran. FAU - Rezayat, Seyed-Mahdi AU - Rezayat SM AD - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. Rezayat@tums.ac.ir. LA - eng PT - Journal Article DEP - 20180824 PL - Switzerland TA - Inflammopharmacology JT - Inflammopharmacology JID - 9112626 RN - 0 (Myd88 protein, rat) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-kappa B) RN - 0 (Receptors, Melatonin) RN - 0 (Tlr4 protein, rat) RN - 0 (Toll-Like Receptor 4) RN - 8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid) RN - JL5DK93RCL (Melatonin) MH - Animals MH - Colitis/chemically induced/*drug therapy/metabolism MH - Colon/drug effects/metabolism MH - Down-Regulation/drug effects MH - Intestinal Mucosa/drug effects/metabolism MH - Male MH - Melatonin/*pharmacology MH - Myeloid Differentiation Factor 88/*metabolism MH - NF-kappa B/*metabolism MH - Rats MH - Rats, Wistar MH - Receptors, Melatonin/*metabolism MH - Signal Transduction/*drug effects MH - Toll-Like Receptor 4/*metabolism MH - Trinitrobenzenesulfonic Acid/pharmacology MH - Up-Regulation/drug effects OTO - NOTNLM OT - Melatonin OT - TLR4/NF-kappaB signalling pathway OT - TNBS OT - Ulcerative colitis EDAT- 2018/08/26 06:00 MHDA- 2019/08/27 06:00 CRDT- 2018/08/26 06:00 PHST- 2017/11/15 00:00 [received] PHST- 2018/02/07 00:00 [accepted] PHST- 2018/08/26 06:00 [pubmed] PHST- 2019/08/27 06:00 [medline] PHST- 2018/08/26 06:00 [entrez] AID - 10.1007/s10787-018-0523-8 [pii] AID - 10.1007/s10787-018-0523-8 [doi] PST - ppublish SO - Inflammopharmacology. 2019 Apr;27(2):361-371. doi: 10.1007/s10787-018-0523-8. Epub 2018 Aug 24.