Premium
Prooxidant Action of Hinokitiol: Hinokitiol‐Iron Dependent Generation of Reactive Oxygen Species
Author(s) -
Murakami Keiko,
Ohara Yoshihiro,
Haneda Miyako,
Tsubouchi Ryoko,
Yoshino Masataka
Publication year - 2005
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2005.pto_214.x
Subject(s) - chemistry , aconitase , reactive oxygen species , superoxide dismutase , superoxide , catalase , biochemistry , antioxidant , enzyme
Hinokitiol (α‐thujaplicin, 2‐hydroxy‐4‐isopropyl‐2,4,6‐cycloheptatrien‐1‐one), one of the tropolone compounds purified from the woods of Chamaecyparis and Thujopsis (hinoki and hiba), produced reactive oxygen species as a complex with transition metals. Hinokitiol/iron complex inactivated aconitase, the most sensitive enzyme to reactive oxygen, whereas it did not affect aldolase and glyceraldehyde 3‐phosphate dehydrogenase. The inactivation of aconitase was iron‐dependent, and prevented by TEMPOL, a scavenger of reactive oxygen species and superoxide dismutase, suggesting that the hinokitiol/iron‐mediated generation of superoxide anion is responsible for the inactivation of aconitase. Addition of hinokitiol effectively enhanced the ascorbate/copper‐mediated formation of 8‐hydroxy‐2′‐deoxyguanosine in DNA. Cytotoxic effect of hinokitiol can be explained by its prooxidant properties: hinokitiol/transition metal complex generates reactive oxygen species causing inactivation of aconitase and production of hydroxyl radical resulting in the formation of DNA base adduct.