Sumatriptan Mitigates Bleomycin-Induced Lung Fibrosis in Male Rats: Involvement of Inflammation, Oxidative Stress and Α-Sma Publisher Pubmed



Bahramifar A^{1, 2} ; Jafari RM^{1, 2} ; Sheibani M^{3, 4} ; Manavi MA^{1, 5} ; Rashidian A^{2, 6} ; Tavangar SM^{7, 8} ; Akbariani M⁵ ; Mohammadi Hamaneh A^{1, 2} ; Goudarzi R⁹ ; Shadboorestan A¹⁰ ; Dehpour AR^{1, 2}
Source: Tissue and Cell Published:2024

Abstract

Introduction: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung condition that produces symptoms including coughing which may cause by excessive accumulation of scar tissue inflammatory and oxidative stress exacerbation. Sumatriptan, utilized for migraine treatment as a selective 5-HT1B/1D receptor agonist, has demonstrated significant anti-inflammatory and antioxidant properties in multiple preclinical investigations. Operating primarily on serotonin receptors, sumatriptan leverages the diverse physiological functions of serotonin, playing a pivotal role in regulating both inflammation and oxidative stress which is particularly relevant in the context of IPF. Materials & methods: Thirty-five male Wistar rats were divided to five group, including: Sham (without IPF induction), control (BLM 5 mg/kg, intraperitoneally), and three fibrosis group with sumatriptan (0.5, 1, and 3 mg/kg, i.p. for 2 weeks) administration. IPF was induced by injection of BLM (single dose, 5 mg/kg intratracheally). Lung tissues were separated for measurement of myeloperoxidase (MPO) as an oxidative stress hallmark, and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-β), and transforming growth factor-β (TGF-β) as inflammatory markers as well as alpha smooth muscle actin (α-SMA). Also, for histological investigations, tissue damages were assessed by Hematoxylin-eosin (H&E) and Masson's trichrome staining method. Results: BLM-induced fibrosis could increase α-SMA, MPO, TNF-α, IL-1β, and TGF-β, while treatment with sumatriptan has reversed the α-SMA, MPO, and IL-1β levels. Moreover, the results of H&E and Masson's trichrome staining indicated that sumatriptan (1 and 3 mg/kg) reduced tissue damages, alveolar wall thickness, collagen accumulation, and pulmonary fibrosis induced by BLM. Conclusion: According to the data achieved from this study, Sumatriptan appears to have therapeutic benefits in IPF, possibly via reducing α-SMA as well as inflammation and the toxicity caused by oxidative stress. © 2024 Elsevier Ltd