Superoxide scavenging activity of pirfenidone-iron complex.
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.
Mitani
Yoshihiro
Y
Division of Pharmacology & Therapeutics, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan.
Sato
Keizo
K
Muramoto
Yosuke
Y
Karakawa
Tomohiro
T
Kitamado
Masataka
M
Iwanaga
Tatsuya
T
Nabeshima
Tetsuji
T
Maruyama
Kumiko
K
Nakagawa
Kazuko
K
Ishida
Kazuhiko
K
Sasamoto
Kazumi
K
D002460:Cell Line; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007501:Iron; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000188:drug therapy; D011728:Pyridones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism*
D016166:Free Radical Scavengers; D011728:Pyridones; D013481:Superoxides; C093844:pirfenidone; D007501:Iron