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Melatonin ameliorates TNBS-induced colitis in rats through the melatonin receptors: involvement of TLR4/MyD88/NF-κB signalling pathway

Inflammopharmacology volume 27, pages 361–371 (2019)Cite this article

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.

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Acknowledgements

This study was resulted from a Ph.D. dissertation supported by Tehran University of Medical Sciences (TUMS), Grant number 9121336003. We wish to thank Dr. Saman Hosseinkhani and Dr. Mohsen Alipour (Tarbiat Modares University, Tehran, Iran) for their excellent technical assistance. Thanks are due to Dr. Vahid Nikoui (Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran) for his invaluable editorial assistance.

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Affiliations

  1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran

    Mohsen Chamanara, Amir Rashidian, Shahram Ejtemaei Mehr, Ahmad-Reza Dehpour, Reyhaneh Akbarian & Seyed-Mahdi Rezayat

  2. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Amir Rashidian & Ahmad-Reza Dehpour

  3. Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran

    Reza Shirkohi

  4. Department of Pathology, Imam Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Alireza Abdollahi

Authors
  1. Mohsen Chamanara
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  2. Amir Rashidian
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  3. Shahram Ejtemaei Mehr
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  4. Ahmad-Reza Dehpour
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  5. Reza Shirkohi
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  6. Reyhaneh Akbarian
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  7. Alireza Abdollahi
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  8. Seyed-Mahdi Rezayat
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Correspondence to Seyed-Mahdi Rezayat.

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Chamanara, M., Rashidian, A., Mehr, S.E. et al. Melatonin ameliorates TNBS-induced colitis in rats through the melatonin receptors: involvement of TLR4/MyD88/NF-κB signalling pathway. Inflammopharmacol 27, 361–371 (2019). https://doi.org/10.1007/s10787-018-0523-8

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Keywords

  • Melatonin
  • Ulcerative colitis
  • TNBS
  • TLR4/NF-κB signalling pathway