Carnitine esters prevent oxidative stress damage and energy depletion following transient forebrain ischaemia in the rat hippocampus
Carnitine esters prevent oxidative stress damage and energy depletion following transient forebrain ischaemia in the rat hippocampus
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DOI：
10.1111/j.1440-1681.2006.04425.x
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发表时间：
2006-08-01
影响因子：
2.9
通讯作者：
Al-Shabanah, Othman A.
中科院分区：
文献类型：
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作者：
Al-Majed, Abdulhakeem A.;Sayed-Ahmed, Mohamed M.;Al-Shabanah, Othman A.
1.本研究探讨丙酰-L-卡尼汀（propionyl-L-carnitine，PLC）是否具有与乙酰-L-卡尼汀（acetyl-L-carnitine，AC）相似的神经保护作用，对抗短暂性前脑缺血引起的大鼠海马CA 1区神经元损伤和生化紊乱.总共将105只成年雄性Wistar白化病大鼠分为7组，每组15只动物。前3组分别腹腔注射生理盐水、AC（300 mg/kg）或PLC（300 mg/kg），连续7 d。在诱导前脑缺血10 min后立即腹腔注射相同剂量的生理盐水、AC或PLC，并连续腹腔注射7 d。第七组大鼠造成假手术缺血，注射生理盐水，连续7天.治疗后7天，处死动物，分离脑组织进行病理组织学检查和生化研究.前脑缺血导致海马组织中完整神经元数量（77%）、ATP浓度（51%）和谷胱甘肽含量（32%）显著减少，而硫代巴比妥酸反应物质（TBARS; 71%）和总硝酸盐/亚硝酸盐（NOx; 260%）的产生显著增加. AC或PLC的给药减弱了前脑缺血诱导的神经元损伤，表现为更多数量的完整神经元、ATP和谷胱甘肽，以及海马组织中TBARS和NOx的减少。本研究的结果表明，第一次，PLC衰减前脑缺血引起的神经元损伤，氧化应激和能量消耗在海马CA 1区。丙酰-L-肉毒碱具有与AC相似的神经保护作用，可能在神经退行性疾病的治疗中具有潜在的用途。本研究的结果将开辟新的前景，使用PLC在治疗相关的神经退行性疾病，或继发于心肌缺血再灌注损伤和慢性循环衰竭。
1. The present study investigated whether propionyl-L-carnitine (PLC) has neuroprotective effects, similar to those reported for acetyl-l-carnitine (AC), against transient forebrain ischaemia-induced neuronal damage and biochemical derangement in the rat hippocampal CA1 region.2. In total, 105 adult male Wistar albino rats were divided into seven groups of 15 animals each. The first three groups were injected i.p. with normal saline, AC (300 mg/kg) or PLC (300 mg/kg) for 7 successive days. The next three groups were injected i.p. with the same doses of normal saline, AC or PLC immediately after the induction of 10 min forebrain ischaemia and i.p. injections were continued for 7 successive days. Rats in the seventh group were subjected to sham-operated ischaemia and injected with normal saline for 7 successive days.3. Seven days after treatment, animals were killed and their brains isolated for histopathological examination and biochemical studies.4. Forebrain ischaemia resulted in a significant decrease in the number of intact neurons (77%), ATP concentration (51%) and glutathione content (32%), whereas there was a significant increase in the production of thiobarbituric acid-reactive substances (TBARS; 71%) and total nitrate/nitrite (NOx; 260%) in hippocampal tissues.5. Administration of either AC or PLC attenuated forebrain ischaemia-induced neuronal damage, manifested by a greater number of intact neurons, ATP and glutathione, as well as a decrease in TBARS and NOx in hippocampal tissues.6. Results from the present study suggest, for the first time, that PLC attenuates forebrain ischaemia-induced neuronal injury, oxidative stress and energy depletion in the hippocampal CA1 region. Propionyl-L-carnitine has neuroprotective effects similar to AC and could have a potential use in the treatment of neurodegenerative diseases.7. The results of the present study will open up new perspectives for the use of PLC in the treatment of neurodegenerative diseases associated with, or secondary to, myocardial ischaemia-reperfusion injury and chronic circulatory failure.