title: Phototoxicity of kava - formation of reactive oxygen species leading to lipid peroxidation and DNA damage.
abstract: Kava is one of the most widely sold herbal dietary supplements in the United States. It has been reported that, besides exhibiting hepatotoxicity, kava also possesses photosensitivity and induces dermopathy in humans. In this study, we determined that UVA irradiation of kava in the presence of a lipid, methyl linoleate, generated lipid peroxidation which was mediated by singlet oxygen generated during photoirradiation. The six major kavalactones(yangonin, 7,8-dihydrokawa in, kawain, 7,8-dihydromethysticin, methysticin, and 5,6-dehydrokawain) were also studied in parallel; only 5,6-dehydrokawain and yangonin-induced a low level of lipid peroxidation. UVA irradiation of kava in human HaCaT skin keratinocytes induced cytotoxicity which was mediated by oxidative stress, led to DNA strand cleavage, and produced 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct. Study by the electron spin resonance (ESR) method revealed that UVA irradiation of kava produced singlet oxygen and carbon-centered radicals. The overall results suggest that kava is photocytotoxic and photogenotoxic, both mediated by free radicals generated during photoirradiation.
authors.affiliation: National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079,  USA.
authors.forename: Qingsu
authors.initials: Q
authors.lastname: Xia
authors.forename: Hsiu-Mei
authors.initials: HM
authors.lastname: Chiang
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Zhou
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Yin
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.forename: Peter P
authors.initials: PP
authors.lastname: Fu
mesh_terms: D002460:Cell Line; D004249:DNA Damage; D004578:Electron Spin Resonance Spectroscopy; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D020901:Kava / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species