Subject(s)
Anti-Bacterial Agents/pharmacology , Enterocolitis, Pseudomembranous/prevention & control , Erythromycin/pharmacology , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Erythromycin/administration & dosage , Erythromycin/therapeutic use , Humans , Interleukin-8/biosynthesisABSTRACT
Pirfenidone (PFD) is focused on a new anti-fibrotic drug, which can minimize lung fibrosis etc. We evaluated the superoxide (O2*-) scavenging activities of PFD and the PFD-iron complex by electron spin resonance (ESR) spectroscopy, luminol-dependent chemiluminescence assay, and cytochrome c reduction assay. Firstly, we confirmed that the PFD-iron complex was formed by mixing iron chloride with threefold molar PFD, and the complex was stable in distilled water and ethanol. Secondary, the PFD-iron complex reduced the amount of O2*- produced by xanthine oxidase/hypoxanthine without inhibiting the enzyme activity. Thirdly, it also reduced the amount of O2*- released from phorbor ester-stimulated human neutrophils. PFD alone showed few such effects. These results suggest the possibility that the O2*- scavenging effect of the PFD-iron complex contributes to the anti-fibrotic action of PFD used for treating idiopathic pulmonary fibrosis.
Subject(s)
Free Radical Scavengers/pharmacology , Pyridones/pharmacology , Superoxides/metabolism , Cell Line , Free Radical Scavengers/chemical synthesis , Free Radical Scavengers/therapeutic use , Humans , Iron , Neutrophils/drug effects , Neutrophils/metabolism , Pulmonary Fibrosis/drug therapy , Pyridones/chemistry , Pyridones/therapeutic use , Superoxides/chemistryABSTRACT
Electron spin resonance using spin-trapping is a useful technique for detecting direct reactive oxygen species, such as superoxide (O2.-). However, the widely used spin trap 2,2-dimethyl-3,4-dihydro-2H-pyrrole N-oxide (DMPO) has several fundamental limitations in terms of half-life and stability. Recently, the new spin trap 2-diphenylphosphinoyl-2-methyl-3,4-dihydro-2H-pyrrole N-oxide (DPhPMPO) was developed by us. We evaluated the biological applicability of DPhPMPO to analyze O2.- in both cell-free and cellular systems. DPhPMPO had a larger rate constant for O2.- and formed more stable spin adducts for O2.- than DMPO in the xanthine/xanthine oxidase (X/XO) system. In the phorbol myristate acetate-activated neutrophil system, the detection potential of DPhPMPO for O2.- was significantly higher than that of DMPO (k(DMPO)=13.95M(-1)s(-1), k(DPhPMPO)=42.4M(-1)s(-1)). These results indicated that DPhPMPO is a potentially good candidate for trapping O2.- in a biological system.
