Fluorescence probes to detect lipid-derived radicals.
Lipids and their metabolites are easily oxidized in chain reactions initiated by lipid radicals, forming lipid peroxidation products that include the electrophiles 4-hydroxynonenal and malondialdehyde. These markers can bind cellular macromolecules, causing inflammation, apoptosis and other damage. Methods to detect and neutralize the initiating radicals would provide insights into disease mechanisms and new therapeutic approaches. We describe the first high-sensitivity, specific fluorescence probe for lipid radicals, 2,2,6-trimethyl-4-(4-nitrobenzo[1,2,5]oxadiazol-7-ylamino)-6-pentylpiperidine-1-oxyl (NBD-Pen). NBD-Pen directly detected lipid radicals in living cells by turn-on fluorescence. In a rat model of hepatic carcinoma induced by diethylnitrosamine (DEN), NBD-Pen detected lipid radical generation within 1 h of DEN administration. The lipid radical scavenging moiety of NBD-Pen decreased inflammation, apoptosis and oxidative stress markers at 24 h after DEN, and liver tumor development at 12 weeks. Thus, we have developed a novel fluorescence probe that provides imaging information about lipid radical generation and potential therapeutic benefits in vivo.
Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.|Japan Science and Technology Agency, PRESTO, Saitama, Japan.
Ken-Ichi
K
Yamada
Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Fumiya
F
Mito
Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yuta
Y
Matsuoka
Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Satsuki
S
Ide
Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Kazushige
K
Shikimachi
Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Ayano
A
Fujiki
Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Daiki
D
Kusakabe
Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yuma
Y
Ishida
Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Masataka
M
Enoki
Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Arisa
A
Tada
Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Miyuki
M
Ariyoshi
Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.|Current address: Aix-Marseille Université, Institut de Chimie Radicalaire, Campus St.-Jérôme, Marseille, France.
Toshihide
T
Yamasaki
Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan.
Mayumi
M
Yamato
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003497:Cyclic N-Oxides / Q000032:analysis* / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D004052:Diethylnitrosamine; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000032:analysis* / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D005609:Free Radicals / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control; D015227:Lipid Peroxidation; D008055:Lipids / Q000737:chemistry*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D013050:Spectrometry, Fluorescence
C000617987:2,2,6-trimethyl-4-(4-nitrobenzo(1,2,5)oxadiazol-7-ylamino)-6-pentylpiperidine-1-oxyl; D003497:Cyclic N-Oxides; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D005609:Free Radicals; D008055:Lipids; D004052:Diethylnitrosamine; D009327:4-Chloro-7-nitrobenzofurazan