Binienda Z, Simmons C, Hussain S, Slikker W, Ali S F
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079, USA.
Neurosci Lett. 1998 Jul 31;251(3):173-6. doi: 10.1016/s0304-3940(98)00539-4.
The response of endogenous antioxidants to acute exposure of the mitochondrial inhibitor, 3-nitropropionic acid (3-NPA), was investigated in selected rat brain regions. Rats treated with 3-NPA (30 mg/kg, s.c.) were sacrificed at 30, 60, 90 and 120 min after injection to examine the alterations in reduced glutathione levels (GSH), and activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the hippocampus (HIP), frontal cortex (FC), and caudate nucleus (CN). CAT activity increased in the HIP 90 min after 3-NPA treatment. While cytosolic copper/zinc SOD (CuZn-SOD) and mitochondrial manganese SOD (Mn-SOD) levels increased in the FC at 120 min, only the Mn-SOD increased in the CN 90 min after treatment. The activity of GPx decreased in the HIP 120 min after 3-NPA injection. When compared with the control, administration of 3-NPA led to GSH depletion in HIP within 120 min. The depletion of GSH and induction of antioxidant enzyme activities after the 3-NPA exposure suggest conditions favorable for oxidative stress.
在选定的大鼠脑区中，研究了内源性抗氧化剂对线粒体抑制剂3-硝基丙酸（3-NPA）急性暴露的反应。用3-NPA（30mg/kg，皮下注射）处理的大鼠在注射后30、60、90和120分钟处死，以检查海马体（HIP）、额叶皮质（FC）和尾状核（CN）中还原型谷胱甘肽水平（GSH）以及抗氧化酶超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和过氧化氢酶（CAT）活性的变化。3-NPA处理90分钟后，海马体中的CAT活性增加。虽然在120分钟时额叶皮质中的胞质铜/锌超氧化物歧化酶（CuZn-SOD）和线粒体锰超氧化物歧化酶（Mn-SOD）水平增加，但处理90分钟后尾状核中仅Mn-SOD增加。3-NPA注射120分钟后，海马体中的GPx活性降低。与对照组相比，给予3-NPA导致120分钟内海马体中的GSH耗竭。3-NPA暴露后GSH的耗竭和抗氧化酶活性的诱导表明存在有利于氧化应激的条件。
