Anti-oxidative effect of the tyrosine kinase inhibitor nintedanib: a potential therapy for chronic lung allograft dysfunction?

Antifibrotic drugs in lung transplantation and chronic lung allograft dysfunction: a review

“…In addition to its antifibrotic effects, animal models demonstrated the ability of pirfenidone to limit alloimmune inflammatory responses by impairing T-cell activation and proliferation, and by inhibiting effects upon dendritic cell activation, maturation and function [31,58,63,64]. Moreover, it exhibits antioxidant properties by scavenging reactive oxygen species and preventing lipid peroxidation [65,66]. These effects have elicited interest in its use as a potential therapeutic agent to prolong allograft survival by inhibiting both fibroproliferative and alloimmune responses [58].…”

“…Antifibrotics in CLAD phenotype BOS BOS is the most common presentation form of CLAD, diagnosed in ∼70% of CLAD patients [52]. The exact pathophysiological mechanism is not yet fully understood, but is widely perceived to be associated with the production of growth factors and inflammatory cytokines, alloimmune processes, non-alloimmune processes and autoimmune processes [65,[67][68][69]. The histological hallmark of BOS is obliterative or constrictive bronchiolitis, which is thought to arise as lymphocytic bronchiolitis, followed by fibroproliferative obliteration of small airways, leading to segmental subtotal or total obliteration of the lumen of small airways (figure 1c).…”

Effects of Pirfenidone and Nintedanib on Markers of Systemic Oxidative Stress and Inflammation in Patients with Idiopathic Pulmonary Fibrosis: A Preliminary Report

“…Although clinical trials have failed to demonstrate a significant improvement in IPF symptoms, antifibrotic therapies improve life expectancy [56]. In addition, both pirfenidone and nintedanib have been shown to exert significant anti-inflammatory and antioxidant effects in vitro however human data are lacking [16,17,19,20]. In our study, 24-week treatment with pirfenidone or nintedanib, when collectively analysed in the whole IPF cohort, significantly increased plasma taurine, GSH and PSH concentrations and reduced kynurenine concentrations.…”

“…More recently, studies have also reported that nintedanib exerts anti-oxidant and anti-inflammatory effects [19,20]. However, the anti-inflammatory and anti-oxidant effects of pirfenidone and nintedanib have been primarily observed in in vitro studies [16][17][18][19][20]. Therefore, we sought to determine the presence of such effects in vivo by investigating a comprehensive panel of markers of OS and inflammation in IPF patients before and after 24-week treatment with pirfenidone or nintedanib and in a group of age-and sex-matched healthy participants.…”

“…Nintedanib is a tyrosine kinase inhibitor with anti-angiogenic effects through the blockade of the vascular endothelial growth factor (VEGF) pathway [18]. More recently, studies have also reported that nintedanib exerts anti-oxidant and anti-inflammatory effects [19,20]. However, the anti-inflammatory and anti-oxidant effects of pirfenidone and nintedanib have been primarily observed in in vitro studies [16][17][18][19][20].…”