P-109 - Functional fluorescence probe for lipid derived radicals detection

Abstract

Lipids are easily oxidized by reactive oxygen species, resulting in lipid peroxidation and metabolic products such as lipid-derived electrophiles. These products have been reported to induce inflammation, angiogenesis and ferroptosis. Here, the initial products of lipid oxidation are lipid-derived radicals, the most upstream products that can cause extensive chain reactions affecting lipid peroxidation. Hence, the ability to detect lipid radicals would provide information about one of most important class of molecules causing cellular and tissue damage in a wide range of diseases. In this study, I will present the first fluorescence probe for lipid radicals, NBD-Pen, with high selectivity and sensitivity. To demonstrate bioavailability of NBD-Pen, we tested it in an animal model in which hepatocellular carcinoma was induced by the hepatic procarcinogen diethylnitrosamine (DEN). Furthermore, we found that lipid radical inhibitor significantly relieved inflammation at the early stage of carcinogenesis, as well as following induction of tumor formation by DEN. Thus, we have developed a novel fluorescence probe that provides imaging information about lipid radical generation and potential therapeutic benefits in vivo.