Introduction: In vitro evidence suggests that pirfenidone and nintedanib, approved agents for the treatment of idiopathic pulmonary fibrosis (IPF), exert anti-inflammatory and anti-oxidant effects. We aimed to investigate such effects in vivo in IPF patients. Methods: Systemic circulating markers of oxidative stress [nuclear factor erythroid 2–related factor 2 (Nrf2), thiobarbituric acid-reactive substances (TBARS), homocysteine (Hcy), cysteine (Cys), asymmetric dimethylarginine (ADMA) and ADMA/Arginine ratio, glutathione (GSH), plasma protein –SH (PSH), and taurine (Tau)] and inflammation [Kynurenine (Kyn), Tryptophan (Trp) and Kyn/Trp ratio] were measured at baseline and after 24-week treatment in 18 IPF patients (10 treated with pirfenidone and 8 with nintedanib) and in 18 age-and sex-matched healthy controls. Results: Compared to controls, IPF patients had significantly lower concentrations of reduced blood GSH (457 ± 73 µmol/L vs 880 ± 212 µmol/L, p < 0.001) and plasma PSH (4.24 ± 0.95 µmol/g prot vs 5.28 ± 1.35 µmol/g prot, p = 0.012). Pirfenidone treatment significantly decreased the Kyn/Trp ratio (0.030 ± 0.011 baseline vs 0.025 ± 0.010 post-treatment, p = 0.048) whilst nintedanib treatment significantly increased blood GSH (486 ± 70 µmol/L vs 723 ± 194 µmol/L, p = 0.006) and reduced ADMA concentrations (0.501 ± 0.094 vs. 0.468 ± 0.071 µmol/L, p = 0.024). Conclusion: pirfenidone and nintedanib exert beneficial effects on specific markers of oxidative stress and inflammation in IPF patients.
Effects of pirfenidone and nintedanib on markers of systemic oxidative stress and inflammation in patients with idiopathic pulmonary fibrosis: A preliminary report / Fois, A. G.; Sotgiu, E.; Scano, V.; Negri, S.; Mellino, S.; Zinellu, E.; Pirina, P.; Pintus, G.; Carru, C.; Mangoni, A. A.; Zinellu, A.. - In: ANTIOXIDANTS. - ISSN 2076-3921. - 9:11(2020), pp. 1-15. [10.3390/antiox9111064]
Effects of pirfenidone and nintedanib on markers of systemic oxidative stress and inflammation in patients with idiopathic pulmonary fibrosis: A preliminary report
Fois A. G.;Sotgiu E.;Scano V.;Negri S.;Mellino S.;Zinellu E.;Pirina P.;Pintus G.;Carru C.;Zinellu A.
2020-01-01
Abstract
Introduction: In vitro evidence suggests that pirfenidone and nintedanib, approved agents for the treatment of idiopathic pulmonary fibrosis (IPF), exert anti-inflammatory and anti-oxidant effects. We aimed to investigate such effects in vivo in IPF patients. Methods: Systemic circulating markers of oxidative stress [nuclear factor erythroid 2–related factor 2 (Nrf2), thiobarbituric acid-reactive substances (TBARS), homocysteine (Hcy), cysteine (Cys), asymmetric dimethylarginine (ADMA) and ADMA/Arginine ratio, glutathione (GSH), plasma protein –SH (PSH), and taurine (Tau)] and inflammation [Kynurenine (Kyn), Tryptophan (Trp) and Kyn/Trp ratio] were measured at baseline and after 24-week treatment in 18 IPF patients (10 treated with pirfenidone and 8 with nintedanib) and in 18 age-and sex-matched healthy controls. Results: Compared to controls, IPF patients had significantly lower concentrations of reduced blood GSH (457 ± 73 µmol/L vs 880 ± 212 µmol/L, p < 0.001) and plasma PSH (4.24 ± 0.95 µmol/g prot vs 5.28 ± 1.35 µmol/g prot, p = 0.012). Pirfenidone treatment significantly decreased the Kyn/Trp ratio (0.030 ± 0.011 baseline vs 0.025 ± 0.010 post-treatment, p = 0.048) whilst nintedanib treatment significantly increased blood GSH (486 ± 70 µmol/L vs 723 ± 194 µmol/L, p = 0.006) and reduced ADMA concentrations (0.501 ± 0.094 vs. 0.468 ± 0.071 µmol/L, p = 0.024). Conclusion: pirfenidone and nintedanib exert beneficial effects on specific markers of oxidative stress and inflammation in IPF patients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
