Fluorescence probes to detect lipid-derived radicals

Abstract

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.

Clinical significance of redox effects of Kampo formulae, a traditional Japanese herbal medicine: comprehensive estimation of multiple antioxidative activities

“…Again, details of the activities of ROO • remain to be clarified, but current research indicates its importance in an animal model of hepatic carcinoma. ( 20 ) Unlike the other ROS, ROO • scavenging activity was notable in formulae whose antioxidative activities were previously unknown, such as saibokuto (SBT), hangekobokuto (HKT) and goreisan (GRS). Because saibokuto (SBT) is a blended formula comprising hangekobokuto (HKT) and shosaikoto (SSK), the components of hangekobokuto (HKT) may relate to ROO • scavenging activity.…”

Photophysical Properties of Emissive Pyrido[3,2‐c]carbazole Derivatives and Apoptosis Induction: Development towards Theranostic Agents in Response to Light Stimulus

“…Therefore, PC-X,c onsisting of pyridocarbazole moieties was examined for organelle accumulation using RedDot, Mitotracker and MitoRed, and LysoTracker Deep Red, which stain nuclei, mitochondria, andl ysosomes, respectively.F igures 5a nd S2 show fluorescencei mages obtained using Ch1-4;t he wavelengths for excitation and emission (excitation/emission) of which are as follows;4 03/450, 403/525, 562/595, and 637/700nmf or Ch1, -2, -3, and -4, respectively. PC-H treatment ( Figure 5) (1). Images captured using alower wavelength for the detection of PC-H are shown in (2).…”

“…Therefore, organelle imaging is of great significance in the field of physiology,b iochemistry,a nd chemical biology. [1][2][3][4][5][6][7] Many dyes have been used for the detection and identification of specific organelles, such as DAPI, Hoechst, and RedDot for nuclei, [8][9][10] MitoTracker and MitoRed for mitochondria, [11,12] and LysoTracker for the lysosomes. [13,14] These dyes have the required structuralf eatures that facilitate accumulationi nt he corresponding organelles.…”

“…Organelle imaging is an essential technique to elucidate organelle function and disease mechanisms. Therefore, organelle imaging is of great significance in the field of physiology, biochemistry, and chemical biology . Many dyes have been used for the detection and identification of specific organelles, such as DAPI, Hoechst, and RedDot for nuclei, MitoTracker and MitoRed for mitochondria, and LysoTracker for the lysosomes .…”

Antioxidant nitroxides protect hepatic cells from oxidative stress-induced cell death

“…( 12 , 13 ) Nitroxides react with many types of species, including ROS ( 14 ) and organic radicals such as lipid radicals generated by lipid oxidation. ( 15 , 16 ) Importantly, nitroxides can react catalytically with oxidative species. Among many reported nitroxide structures, 4-hydroxy-2,2,6,6-tetramethylpiperidyl-1-oxyl (tempol) is the most widely used experimentally because of its high antioxidative activity and low toxic effects.…”