Mirtazapine, an atypical antidepressant, mitigates lung fibrosis by suppressing NLPR3 inflammasome and fibrosis-related mediators in endotracheal bleomycin rat model

Abdelhady, Rasha; Cavalu, Simona; Saber, Sameh; Elmowafy, Rasha; Morsy, Nesreen Elsayed; Ibrahim, Samar; Abdeldaiem, Mahmoud Said Ibrahim; Samy, Mervat; Abdel-Dayem, Marwa A.; Shata, Ahmed; Elgharabawy, Rehab Mohamed

doi:10.1016/j.biopha.2023.114553

Cited by 6 publications

(3 citation statements)

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“…IPF is a chronic progressive disease with the development of interstitial fibrosis and progressive respiratory failure [ 2 , 31 ]. In most cases, the prognosis of IPF is unfavorable, with an average life expectancy of about five years from diagnosis [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

“…The median survival of patients with IPF is 3-5 years [5]. Fibrogenesis in IPF is known to be mainly mediated by abnormal release of profibrogenic factors such as tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β), which promote myofibroblast differentiation/activation, transforming growth factor-beta (TGF-β) [2] and extracellular matrix (ECM) deposition [6]. Levels of the profibrotic cytokine TGF-β directly correlate with the Life 2023, 13,1932 2 of 21 severity of IPF disease [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…Interstitial lung disease (ILD) is a heterogeneous group of diffuse parenchymal processes in the lung characterized by varying degrees of inflammation and fibrosis. Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of ILD (accounting for 20–30% of all ILD cases), and is characterized by progressive parenchymal fibrosis with a poor prognosis [ 1 , 2 ]. Currently, the incidence and prevalence of IPF are increasing worldwide [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Anti-Inflammatory and Antifibrotic Potential of Longidaze in Bleomycin-Induced Pulmonary Fibrosis

Pakhomova,

Pershina,

Bochkov

et al. 2023

Life

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Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease, characterized by progressive parenchymal fibrosis and respiratory failure. In a model of bleomycin-induced pulmonary fibrosis, the antifibrotic and anti-inflammatory activity of Longidaze (Bovhyaluronidase Azoxymer), which contains a conjugate of the hyaluronidase enzyme with a high molecular weight synthetic carrier azoxymer bromide, was investigated. Experiments were conducted in male C57BL/6 mice. Longidaze was administered at different doses by intranasal and intramuscular routes. Histology, hematology, and enzyme-linked immunosorbent assay were used in the study. The use of Longidaze reduced pulmonary fibrosis, as evidenced by an improvement in histopathologic damage to the lungs, a decrease in the area of connective tissue, and the levels of profibrotic factors (TGF-β1, hydroxyproline, collagen I) in lung tissue. In addition, Longidaze inhibited the inflammatory response in pulmonary fibrosis, and decreased the levels of IL-6, TNF-α, and hyaluronic acid in lung tissue and the recruitment of inflammatory cells into lung tissue. The highest therapeutic efficacy was observed with the use of Longidaze at doses of 120 and 1200 U/kg intramuscularly, which was superior to that of the reference drug pirfenidone axunio. The data presented in this study suggest that Longidaze is a new and promising drug for the treatment of IPF that warrants further investigation in patients with fibrotic interstitial lung disease.

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Section: Discussionmentioning

confidence: 99%