TY - JOUR
T1 - Detection and inhibition of lipid-derived radicals in low-density lipoprotein
AU - Ishida, Yuma
AU - Okamoto, Yuka
AU - Matsuoka, Yuta
AU - Tada, Arisa
AU - Janprasit, Jindaporn
AU - Yamato, Mayumi
AU - Morales, Noppawan Phumala
AU - Yamada, Ken Ichi
N1 - Funding Information:
This work was supported in part by JST PRESTO grant number JPMJPR1337 , JSPS KAKENHI grant numbers 16H01363 and 16K15109 , the Platform Project for Supporting Drug Discovery and Life Science Research from the AMED, the Naito Foundation , and the ONO Medical Research Foundation , Japan; and by the Office of the Higher Education Commission and Mahidol University under the National Research Universities Initiative. We appreciate the technical support provided by the Research Support Center, Graduate School of Medical Sciences, Kyushu University, Japan and a support from Development and Promotion of Science and Technology Talents Projects (DPST), Thailand to JJ.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/12
Y1 - 2017/12
N2 - Oxidized low density lipoprotein (Ox-LDL) is implicated in a variety of oxidative diseases. To clarify the mechanisms involved and facilitate the investigation of therapeutics, we previously developed a detection method for lipid-derived radicals using the fluorescent probe 2,2,6-trimethyl-6-pentyl-4-(4-nitrobenzo[1,2,5]oxadiazol-7-ylamino)piperidine-1-oxyl (NBD-Pen). In this study, NBD-Pen was used to detect lipid-derived radicals in Ox-LDL from in vitro and in vivo samples using an iron overloaded mouse model. By following the timeline of lipid radical generation using this method, the iron overloaded mice could be successfully treated with the antioxidant Trolox, resulting in successful lowering of the plasma lipid peroxidation, aspartate transaminase and alanine transaminase levels. Furthermore, using a combination therapy of the chelating agent deferoxamine (DFX) and Trolox, liver injury and oxidative stress markers were also reduced in iron overloaded mice. The NBD-Pen method is highly sensitive as well as selective and is suitable for targeting minimally modified LDL compared with other existing methods.
AB - Oxidized low density lipoprotein (Ox-LDL) is implicated in a variety of oxidative diseases. To clarify the mechanisms involved and facilitate the investigation of therapeutics, we previously developed a detection method for lipid-derived radicals using the fluorescent probe 2,2,6-trimethyl-6-pentyl-4-(4-nitrobenzo[1,2,5]oxadiazol-7-ylamino)piperidine-1-oxyl (NBD-Pen). In this study, NBD-Pen was used to detect lipid-derived radicals in Ox-LDL from in vitro and in vivo samples using an iron overloaded mouse model. By following the timeline of lipid radical generation using this method, the iron overloaded mice could be successfully treated with the antioxidant Trolox, resulting in successful lowering of the plasma lipid peroxidation, aspartate transaminase and alanine transaminase levels. Furthermore, using a combination therapy of the chelating agent deferoxamine (DFX) and Trolox, liver injury and oxidative stress markers were also reduced in iron overloaded mice. The NBD-Pen method is highly sensitive as well as selective and is suitable for targeting minimally modified LDL compared with other existing methods.
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U2 - 10.1016/j.freeradbiomed.2017.10.388
DO - 10.1016/j.freeradbiomed.2017.10.388
M3 - Article
C2 - 29107744
AN - SCOPUS:85032684862
VL - 113
SP - 487
EP - 493
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -