A Review of Pirfenidone as an Anti-Fibrotic in Idiopathic Pulmonary Fibrosis and Its Probable Role in Other Diseases

Shah, Palak; Balani, Prachi; Lopez, Angel R; Nobleza, Chelsea Mae N; Siddiqui, Mariah; Khan, Safeera

doi:10.7759/cureus.12482

Cited by 21 publications

(24 citation statements)

References 31 publications

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“…As far as therapy against Hh signaling, targeting of Smo either genetically by siRNA or pharmacologically via the small molecule inhibitor LDE223 in two SSc mouse models was reported not only to prevent dermal thickening, myofibroblast differentiation and accumulation of collagen, but also to regress established fibrosis [ 172 ]. Moreover, the synthetic molecule pirfenidone, recently approved for the treatment of idiopathic pulmonary fibrosis [ 173 ], was demonstrated to inhibit lung fibrosis by blocking both Hh [ 174 , 175 ] and TGF-β signaling [ 176 , 177 ]. Nevertheless, in a randomized clinical trial, therapeutic use of pirfenidone in SSc patients with ILD had no beneficial effects on disease outcomes [ 178 ].…”

Section: Main Molecular Pathways Driving Myofibroblast Differentiation From Vascular Wall Residing Cells In Systemic Sclerosis and Relatementioning

confidence: 99%

New Insights into Profibrotic Myofibroblast Formation in Systemic Sclerosis: When the Vascular Wall Becomes the Enemy

Romano

Rosa

Fioretto

et al. 2021

Life

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In systemic sclerosis (SSc), abnormalities in microvessel morphology occur early and evolve into a distinctive vasculopathy that relentlessly advances in parallel with the development of tissue fibrosis orchestrated by myofibroblasts in nearly all affected organs. Our knowledge of the cellular and molecular mechanisms underlying such a unique relationship between SSc-related vasculopathy and fibrosis has profoundly changed over the last few years. Indeed, increasing evidence has suggested that endothelial-to-mesenchymal transition (EndoMT), a process in which profibrotic myofibroblasts originate from endothelial cells, may take center stage in SSc pathogenesis. While in arterioles and small arteries EndoMT may lead to the accumulation of myofibroblasts within the vessel wall and development of fibroproliferative vascular lesions, in capillary vessels it may instead result in vascular destruction and formation of myofibroblasts that migrate into the perivascular space with consequent tissue fibrosis and microvessel rarefaction, which are hallmarks of SSc. Besides endothelial cells, other vascular wall-resident cells, such as pericytes and vascular smooth muscle cells, may acquire a myofibroblast-like synthetic phenotype contributing to both SSc-related vascular dysfunction and fibrosis. A deeper understanding of the mechanisms underlying the differentiation of myofibroblasts inside the vessel wall provides the rationale for novel targeted therapeutic strategies for the treatment of SSc.

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Section: Main Molecular Pathways Driving Myofibroblast Differentiation From Vascular Wall Residing Cells In Systemic Sclerosis and Relatementioning

confidence: 99%

New Insights into Profibrotic Myofibroblast Formation in Systemic Sclerosis: When the Vascular Wall Becomes the Enemy

Romano

Rosa

Fioretto

et al. 2021

Life

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“…Besides, the antioxidant effect of PFN may mitigate acute inflammatory reactions and late pulmonary fibrosis in Covid-19 patients through inhibition of NLRP3 inflammasome and NF-κB signaling pathway (Shah et al 2021 ). Rasooli et al ( 2020 ) disclosed that antioxidant agents like vitamin E intensify the antioxidant effect of PFN in the mitigation of pulmonary fibrosis caused by parquets.…”

Section: Role Of Pirfenidone In Post-covid-19 Pulmonary Fibrosismentioning

confidence: 99%

Pirfenidone and post-Covid-19 pulmonary fibrosis: invoked again for realistic goals

Al-Kuraishy¹,

Batiha

Faidah

et al. 2022

Inflammopharmacol

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Pirfenidone (PFN) is an anti-fibrotic drug with significant anti-inflammatory property used for treatment of fibrotic conditions such as idiopathic pulmonary fibrosis (IPF). In the coronavirus disease 2019 (Covid-19) era, severe acute respiratory syndrome 2 (SARS-CoV-2) could initially lead to acute lung injury (ALI) and in severe cases may cause acute respiratory distress syndrome (ARDS) which is usually resolved with normal lung function. However, some cases of ALI and ARDS are progressed to the more severe critical stage of pulmonary fibrosis commonly named post-Covid-19 pulmonary fibrosis which needs an urgent address and proper management. Therefore, the objective of the present study was to highlight the potential role of PFN in the management of post-Covid-19 pulmonary fibrosis. The precise mechanism of post-Covid-19 pulmonary fibrosis is related to the activation of transforming growth factor beta (TGF-β1), which activates the release of extracellular proteins, fibroblast proliferation, fibroblast migration and myofibroblast conversion. PFN inhibits accumulation and recruitment of inflammatory cells, fibroblast proliferation, deposition of extracellular matrix in response to TGFβ1 and other pro-inflammatory cytokines. In addition, PFN suppresses furin (TGFβ1 convertase activator) a protein effector involved in the entry of SARS-CoV-2 and activation of TGFβ1, and thus PFN reduces the pathogenesis of SARS-CoV-2. Besides, PFN modulates signaling pathways such as Wingless/Int (Wnt/β-catenin), Yes-Associated Protein (YAP)/Transcription Co-Activator PDZ Binding Motif (TAZ) and Hippo Signaling Pathways that are involved in the pathogenesis of post-Covid-19 pulmonary fibrosis. In conclusion, the anti-inflammatory and anti-fibrotic properties of PFN may attenuate post-Covid-19 pulmonary fibrosis.

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“…primary sclerosing cholangitis, neurofibromatosis). Pirfenidone exerted antifibrotic, anti-inflammatory, and anti-oxidant effects because it inhibits NADPH-dependent microsomal lipid peroxidation and scavenges hydroxyl radicals [34,35] For: In patients with idiopathic and postadaptive focal segmental glomerulosclerosis treated with pirfenidone, an improvement of GFR with no effect on proteinuria was demonstrated [36].…”

Section: Pirfenidonementioning

confidence: 99%

Oxidative stress mechanisms as potential therapeutic targets in chronic kidney disease

Dobrek¹

2022

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Chronic kidney disease (CKD) is a gradual loss of kidney function over time, leading to the development of kidney failure. CKD is a consequence of common civilization diseases, such as arterial hypertension and diabetes, as well as primary kidney and urinary tract diseases of various aetiologies. The pathogenesis of CKD is complex, and the ongoing inflammation and increased oxidative stress (OS) in kidney tissues also play a significant role in the CKD pathophysiological description. Hence, attempts are being made to pharmacologically modify these important pathophysiological pathways. This article presents a brief overview of the aetiopathogenesis of OS in the course of CKD and briefly lists the research on the novel compounds with expected OS-alleviating activity in CKD based on their interference with selected pathophysiological pathways (xanthine oxidase inhibitors, nicotinamide adenine dinucleotide phosphate oxidase inhibitors, protein kinase C inhibitors, transforming growth factor β inhibitors, or activators of nuclear factor erythroid 2-related factor 2). StreszczeniePrzewlekła choroba nerek (PChN) to postępująca utrata funkcji nerek, prowadząca do rozwoju niewydolności nerek. Przewlekła choroba nerek stanowi obecnie narastający globalny problem zdrowotny, ponieważ jest następstwem powszechnie występujących chorób cywilizacyjnych, takich jak nadciśnienie tętnicze i cukrzyca, a także pierwotnych chorób nerek i dróg moczowych o różnej etiologii. Patogeneza PChN jest złożona, a wzajemnie podtrzymujące się lokalny stan zapalny i zwiększony stres oksydacyjny w tkankach nerek również odgrywają istotną rolę w opisie patofizjologicznym PChN. W związku z tym podejmowane są próby modulacji farmakologicznej tych ważnych szlaków patofizjologicznych. W artykule przedstawiono zarys etiopatogenezy stresu oksydacyjnego w przebiegu PChN oraz pokrótce wymieniono badania nad nowymi związkami o spodziewanym działaniu łagodzącym wspomniane zaburzenie w wyniku ich ingerencji w patomechanizmy stresu oksydacyjnego (inhibitory oksydazy ksantynowej, inhibitory oksydazy fosforanu dinukleotydu nikotynamidoadeninowego, inhibitory kinazy białkowej C, inhibitory transformującego czynnika wzrostu β lub aktywatory szlaków zależnych od czynnika transkrypcyjnego Nrf2).

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A Review of Pirfenidone as an Anti-Fibrotic in Idiopathic Pulmonary Fibrosis and Its Probable Role in Other Diseases

Cited by 21 publications

References 31 publications

New Insights into Profibrotic Myofibroblast Formation in Systemic Sclerosis: When the Vascular Wall Becomes the Enemy

New Insights into Profibrotic Myofibroblast Formation in Systemic Sclerosis: When the Vascular Wall Becomes the Enemy

Pirfenidone and post-Covid-19 pulmonary fibrosis: invoked again for realistic goals

Oxidative stress mechanisms as potential therapeutic targets in chronic kidney disease

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