Inhibitory Effects of Dutasteride on TLR4: An In vitro Pain Study

Leila Taheran; Hakimeh Zali; Kazem Sharifi; Mohsen Yazdani; Mohammad Ajoudanian; Mir-shahram Safari; Samira Rajaei; Ali Dabbagh

doi:10.18502/ijaai.v21i5.11044

Leila Taheran Anesthesiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Hakimeh Zali Department of Tissue Engineering, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Kazem Sharifi Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Mohsen Yazdani Department of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
Mohammad Ajoudanian Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Mir-shahram Safari Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Samira Rajaei Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Ali Dabbagh Anesthesiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v21i5.11044

Keywords: Dutasteride; Neuropathic pain; Toll-like receptor 4

Abstract

Dutasteride was potentially proposed to control chronic pain by Toll-Like Receptor 4 (TLR4) inhibition through its effect on TLR4 expression, Myeloid differentiation primary response 88 (MyD88), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), secretory Interleukin-1β (IL-1β), and nitric oxide (NO) in the Lipopolysaccharides (LPS)-stimulated U-87 MG cell line.

The human astrocytoma U-87 MG cell line was cultured and incubated with 10 μg/mL of LPS for 24 hours to create a neuro-inflammation model, using two different treatment approaches. The first approach included LPS treatment for 24 hours, followed by dutasteride (20 μg/mL) incubation for the next 72 hours. In the second treatment approach, the cells were co-incubated with LPS and dutasteride for 72 hours. Expression of TLR4, MyD88, NF-κBp65, and secretory IL-1 was evaluated by Western blotting while expression of NO was assessed by NO assay.

TLR4, MyD88, NF-κBp65, and secretory IL-1β levels increased in LPS-treated cells after 24 hours. Dutasteride significantly decreased the secretion of NO and also, the levels of TLR4, MyD88, and NF-κBp65 in both treatment approaches. No difference in IL-1β level was seen with the second treatment approach.

Dutasteride has anti-inflammatory properties and probably analgesic effects, by mechanisms different from conventional analgesics.