Yalcin Ayfer, Kilinc Emrah, Kocturk Semra, Resmi Halil, Sozmen Eser Y
Department of Biochemistry, Faculty of Pharmacy, Ege University, Izmir, Turkey.
Int J Neurosci. 2004 Sep;114(9):1085-97. doi: 10.1080/00207450490475535.
Oxidative stress is a likely molecular mechanism in the neurotoxicity of kainic acid (KA), an excitotoxic substance. The aim of this report was to assess the effect of melatonin co-treatment against KA by measuring the levels of Coenzyme Q10 (CoQ 10), lipid peroxidation (LPO), and Thioredoxin (Trx) mRNA in the rat hippocampus. The male rats were divided into three groups as saline, KA treatment (15 mg/kg), and KA plus melatonin (20 mg/kg). The levels of LPO and CoQ10 were determined by high pressure liquid chromatography (HPLC) consisting of fluorescence and electro-chemical detectors, respectively. The expression of the Trx gene was quantified using reverse transcription followed by real-time polymerase chain reaction (RT-PCR). The results show that the level of LPO increased although the level of CoQ10 decreased both in homogenates and mitochondria in KA-treated rats However, melatonin co-treatment attenuated the level of LPO and partially restored the level of CoQ10. Melatonin co-treatment against KA did not affect the regulation of Trx. Finally, in the context of the decreased LPO and the increased CoQ10, the results suggest that melatonin may be protective against central nervous system pathologies involving excitotoxicity or where oxidative damage may contribute to mitochondrial dysfunction.
氧化应激可能是兴奋性毒性物质海藻酸(KA)神经毒性的分子机制。本报告的目的是通过测量大鼠海马体中辅酶Q10(CoQ10)、脂质过氧化(LPO)和硫氧还蛋白(Trx)mRNA的水平,评估褪黑素联合治疗对KA的影响。雄性大鼠分为三组:生理盐水组、KA治疗组(15毫克/千克)和KA加褪黑素组(20毫克/千克)。LPO和CoQ10的水平分别通过配备荧光和电化学检测器的高压液相色谱(HPLC)测定。Trx基因的表达通过逆转录随后进行实时聚合酶链反应(RT-PCR)进行定量。结果表明,KA处理的大鼠匀浆和线粒体中LPO水平升高,而CoQ10水平降低。然而,褪黑素联合治疗降低了LPO水平,并部分恢复了CoQ10水平。褪黑素联合治疗KA对Trx的调节没有影响。最后,在LPO降低和CoQ10升高的情况下,结果表明褪黑素可能对涉及兴奋性毒性或氧化损伤可能导致线粒体功能障碍的中枢神经系统疾病具有保护作用。