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Superoxide scavenging activity of pirfenidone-iron complex
Authors:Mitani Yoshihiro  Sato Keizo  Muramoto Yosuke  Karakawa Tomohiro  Kitamado Masataka  Iwanaga Tatsuya  Nabeshima Tetsuji  Maruyama Kumiko  Nakagawa Kazuko  Ishida Kazuhiko  Sasamoto Kazumi
Institution:a Division of Pharmacology & Therapeutics, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan
b Dojindo Laboratories, Kumamoto, Japan
c Dojin Glocal Corporation, Kumamoto, Japan
Abstract:Pirfenidone (PFD) is focused on a new anti-fibrotic drug, which can minimize lung fibrosis etc. We evaluated the superoxide (View the MathML source) 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 View the MathML source produced by xanthine oxidase/hypoxanthine without inhibiting the enzyme activity. Thirdly, it also reduced the amount of View the MathML source released from phorbor ester-stimulated human neutrophils. PFD alone showed few such effects. These results suggest the possibility that the View the MathML source scavenging effect of the PFD-iron complex contributes to the anti-fibrotic action of PFD used for treating idiopathic pulmonary fibrosis.
Keywords:2  2-Dimethyl-3  4-dihydro-2H-pyrrole N-oxide (DMPO)  Free radical  Electron spin resonance  Xanthine oxidase  Neutrophil
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