Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 372, Issue 1, Pages 19-23Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.04.093
Keywords
2,2-dimethyl-3,4-dihydro-2H-pyrrole N-oxide (DMPO); free radical; electron spin resonance; xanthine oxidase; neutrophil
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Pirfenidone (PFD) is focused on a new anti-fibrotic drug, which can minimize lung fibrosis etc. We evaluated the superoxide (O-2(center dot-)) 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 distillated water and ethanol. Secondary, the PFD-iron complex reduced the amount of O-2(center dot-) produced by xanthine oxidase/hypoxanthine without inhibiting the enzyme activity. Thirdly, it also reduced the amount of O-2(center dot-) released from phorbor ester-stimulated human neutrophils. PFD alone showed few such effects. These results suggest the possibility that the O-2(center dot-) scavenging effect of the PFD-iron complex contributes to the anti-fibrotic action of PFD used for treating idiopathic pulmonary fibrosis. (C) 2008 Elsevier Inc. All rights reserved.
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