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3‐butyl‐6‐fluoro‐1 (3H)‐isobenzofuranone, a derivative of dl ‐ n ‐butylphthalide, attenuates hydrogen peroxide‐induced damage in PC12 cells
Author(s) -
Xu Ling,
Ji MengXue,
Zhao Na,
Ji BianSheng
Publication year - 2011
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20393
Subject(s) - nitric oxide , hydrogen peroxide , chemistry , malondialdehyde , reactive oxygen species , cytotoxicity , pharmacology , glutathione , glutathione peroxidase , nitric oxide synthase , intracellular , biochemistry , oxidative stress , enzyme , medicine , in vitro , organic chemistry
Abstract The anti‐cerebral ischemia agent, dl ‐3‐ n ‐butylphthalide (NBP), is effective in models of vascular dementia in animals. The present study investigates the protective effect of 3‐butyl‐6‐fluoro‐1 (3H)‐isobenzofuranone (6‐F‐NBP), a fluoro derivative of dl ‐ n butylphthalide, in hydrogen peroxide (H 2 O 2 )‐induced damage in PC12 cells. Exposure of PC12 cells to H 2 O 2 for 24 h led to decreased cell survival, glutathione peroxidase (GSH‐PX), and mitochondrial membrane potential (MMP). In contrast, malondialdehyde (MDA) production, nitric oxide synthase (NOS) activity, nitric oxide (NO) formation, and intracellular reactive oxygen species (ROS) were increased, as was intracellular accumulation of [Ca 2+ ] i . However, pretreatment with 6‐F‐NBP markedly reversed the changes induced by H 2 O 2 , exhibiting a protective effect against H 2 O 2 ‐induced cytotoxicity in PC12 cells. The compound may have therapeutic potential in the treatment of cerebral ischemia by inhibiting the oxidative damage. Drug Dev Res 72: 259–264, 2011. © 2010 Wiley‐Liss, Inc.