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

被引:30
作者
Fois, Alessandro G. [1 ]
Sotgiu, Elisabetta [2 ]
Scano, Valentina [1 ]
Negri, Silvia [1 ]
Mellino, Sabrina [2 ]
Zinellu, Elisabetta [3 ]
Pirina, Pietro [1 ]
Pintus, Gianfranco [2 ,4 ,5 ]
Carru, Ciriaco [2 ]
Mangoni, Arduino A. [6 ,7 ]
Zinellu, Angelo [2 ]
机构
[1] Univ Sassari, Dept Med Surg & Expt Sci, I-07100 Sassari, Italy
[2] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy
[3] Univ Hosp Sassari AOU, Unit Resp Dis, I-07100 Sassari, Italy
[4] Univ Sharjah, Coll Hlth Sci, Dept Med Lab Sci, POB 27272, Sharjah, U Arab Emirates
[5] Univ Sharjah, Sharjah Inst Med Res, POB 27272, Sharjah, U Arab Emirates
[6] Flinders Univ S Australia, Coll Med & Publ Hlth, Dept Clin Pharmacol, Adelaide, SA 5100, Australia
[7] Flinders Med Ctr, Adelaide, SA 5100, Australia
关键词
idiopathic pulmonary fibrosis; inflammation; nintedanib; oxidative stress; pirfenidone; LOWER RESPIRATORY-TRACT; CAPILLARY-ELECTROPHORESIS; GLUTATHIONE DEFICIENCY; LUNG; PATHOGENESIS; DIAGNOSIS; TAURINE; PLASMA; NRF2; GUIDELINES;
D O I
10.3390/antiox9111064
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu mol/L vs 880 +/- 212 mu mol/L, p < 0.001) and plasma PSH (4.24 +/- 0.95 mu mol/g prot vs 5.28 +/- 1.35 mu mol/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 mu mol/L vs 723 +/- 194 mu mol/L, p = 0.006) and reduced ADMA concentrations (0.501 +/- 0.094 vs. 0.468 +/- 0.071 mu mol/L, p = 0.024). Conclusion: pirfenidone and nintedanib exert beneficial effects on specific markers of oxidative stress and inflammation in IPF patients.
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页码:1 / 15
页数:15
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