Venkataraman Prabhu, Krishnamoorthy Gunasekaran, Vengatesh Ganapathy, Srinivasan Narasimhan, Aruldhas Maria Michael, Arunakaran Jagadeesan
Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, India.
Int J Dev Neurosci. 2008 Oct;26(6):585-91. doi: 10.1016/j.ijdevneu.2008.05.002. Epub 2008 May 9.
Polychlorinated biphenyls (PCBs) are one of the environmental toxicants and neurotoxic compounds which induce the production of free radicals leading to oxidative stress. Membrane proteins that control ion gradients across organellar and plasma membranes appear to be particularly susceptible to oxidation induced changes. Melatonin plays an important role in neurodegenerative diseases as an antioxidant and neuroprotector. The aim of this study was to determine the protective role of melatonin on PCB (Aroclor 1254) induced changes in activities of membrane bound ATPases and acetylcholine esterase in selected brain regions of adult rats. Group I: rats intraperitoneally (i.p.) administered corn oil (vehicle) for 30 days. Group II: rats injected i.p. with Aroclor 1,254 (PCB) at 2mg/kg bw/day for 30 days. Groups III and IV: rats intraperitoneally received melatonin (5 or 10mg/kg bw/day) simultaneously with Aroclor 1,254 for 30 days. Groups V and VI: rats intraperitoneally received melatonin (5 or 10mg/kg bw/day) alone for 30 days. After 30 days, rats were sacrificed and the brain regions were dissected to cerebral cortex (Cc), cerebellum (C) and hippocampus (H). Lipid peroxidation (LPO), hydrogen peroxide (H(2)O(2)), hydroxyl radical (OH) and the activities of Na(+)K(+) ATPase, Ca(2+) ATPase, Mg(2+) ATPase and acetyl cholinesterase were determined. Reduced glutathione (GSH) level was also determined. Melatonin levels in serum was measured by enzyme labeled immunosorbent assay (ELISA). Activities of all the enzymes and GSH level were decreased while an increase in H(2)O(2), OH and LPO were observed in brain regions of PCB treated animals. Melatonin levels in serum was decreased in PCB exposed animals. Exogenous melatonin supplementation retrieved all the parameters, significantly. These results suggest that PCB alters membrane bound ATPases and cholinergic function by inducing oxidative stress in brain regions, which can be protected by melatonin.
多氯联苯(PCBs)是环境毒物和神经毒性化合物之一,可诱导自由基产生,导致氧化应激。控制细胞器膜和质膜上离子梯度的膜蛋白似乎特别容易受到氧化诱导的变化影响。褪黑素作为一种抗氧化剂和神经保护剂,在神经退行性疾病中发挥着重要作用。本研究的目的是确定褪黑素对成年大鼠选定脑区中多氯联苯(Aroclor 1254)诱导的膜结合ATP酶和乙酰胆碱酯酶活性变化的保护作用。第一组:大鼠腹腔注射玉米油(赋形剂)30天。第二组:大鼠腹腔注射Aroclor 1,254(多氯联苯),剂量为2mg/kg体重/天,持续30天。第三组和第四组:大鼠腹腔注射褪黑素(5或10mg/kg体重/天),同时注射Aroclor 1,254,持续30天。第五组和第六组:大鼠腹腔注射褪黑素(5或10mg/kg体重/天),单独注射30天。30天后,处死大鼠,解剖脑区,取大脑皮层(Cc)、小脑(C)和海马体(H)。测定脂质过氧化(LPO)、过氧化氢(H₂O₂)、羟自由基(OH)以及Na⁺K⁺ATP酶、Ca²⁺ATP酶、Mg²⁺ATP酶和乙酰胆碱酯酶的活性。还测定了还原型谷胱甘肽(GSH)水平。通过酶联免疫吸附测定(ELISA)测量血清中的褪黑素水平。在多氯联苯处理动物的脑区中,所有酶的活性和GSH水平均降低,而H₂O₂、OH和LPO则升高。暴露于多氯联苯的动物血清中的褪黑素水平降低。外源性补充褪黑素显著恢复了所有参数。这些结果表明,多氯联苯通过在脑区诱导氧化应激来改变膜结合ATP酶和胆碱能功能,而褪黑素可以对此起到保护作用。