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氧化应激改变多氯联苯(Aroclor 1254)暴露大鼠血清和脑区中的肌酸激酶系统:褪黑素的保护作用。

Oxidative stress alters creatine kinase system in serum and brain regions of polychlorinated biphenyl (Aroclor 1254)-exposed rats: protective role of melatonin.

作者信息

Venkataraman Prabhu, Krishnamoorthy Gunasekaran, Selvakumar Kandaswamy, Arunakaran Jagadeesan

机构信息

Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India.

出版信息

Basic Clin Pharmacol Toxicol. 2009 Aug;105(2):92-7. doi: 10.1111/j.1742-7843.2009.00406.x. Epub 2009 Mar 27.

Abstract

Polychlorinated biphenyls are one of the environmental toxicants and neurotoxic compounds which induce the production of free radicals. Creatine kinase plays a key role in energy metabolism of nervous tissue and might be one of the targets for reactive oxygen species. Melatonin, an indoleamine, plays an important role in neurodegenerative diseases as an antioxidant and neuroprotector. The objective of the present study was to investigate the protective role of melatonin on polychlorinated biphenyl (Aroclor 1254)-induced oxidative stress and the changes in creatine kinase activity in brain regions of adult rats. Group I: rats were intraperitoneally (i.p.) administered with corn oil (vehicle) for 30 days. Group II: rats injected i.p. with Aroclor 1254 at 2 mg/kg body weight (bw)/day for 30 days. Groups III and IV: rats i.p. received melatonin (5 or 10 mg/kg bw/day) simultaneously with Aroclor 1254 for 30 days. After 30 days, rats were killed and the brain regions were dissected to cerebral cortex, cerebellum and hippocampus. Lipid peroxidation, hydroxyl radical and hydrogen peroxide (H2O2) levels were determined. The activity of creatine kinase was assayed in serum and brain regions, and its isoenzymes in serum were separated electrophoretically. Activity of creatine kinase was decreased while an increase in H2O2, hydroxyl radical and lipid peroxidation was observed in brain regions of polychlorinated biphenyl-treated rats. Also polychlorinated biphenyl exposure showed a significant increase in serum creatine kinase level and its isoforms such as BB-creatine kinase, MB-creatine kinase, and MM-creatine kinase. Administration of melatonin prevented these alterations induced by polychlorinated biphenyl by its free radical scavenging mechanism. Thus, polychlorinated biphenyl alters creatine kinase activity by inducing oxidative stress in brain regions, which can be protected by melatonin.

摘要

多氯联苯是环境毒物和神经毒性化合物之一,可诱导自由基的产生。肌酸激酶在神经组织的能量代谢中起关键作用,可能是活性氧的作用靶点之一。褪黑素是一种吲哚胺,作为抗氧化剂和神经保护剂,在神经退行性疾病中发挥重要作用。本研究的目的是探讨褪黑素对多氯联苯(Aroclor 1254)诱导的成年大鼠脑区氧化应激及肌酸激酶活性变化的保护作用。第一组:大鼠腹腔注射玉米油(溶剂)30天。第二组:大鼠腹腔注射Aroclor 1254,剂量为2 mg/kg体重/天,共30天。第三组和第四组:大鼠在腹腔注射Aroclor 1254的同时,腹腔注射褪黑素(5或10 mg/kg体重/天),共30天。30天后,处死大鼠,将脑区解剖为大脑皮层、小脑和海马体。测定脂质过氧化、羟自由基和过氧化氢(H₂O₂)水平。检测血清和脑区肌酸激酶的活性,并用电泳法分离血清中的同工酶。多氯联苯处理的大鼠脑区肌酸激酶活性降低,同时H₂O₂、羟自由基和脂质过氧化增加。多氯联苯暴露还使血清肌酸激酶水平及其同工型如BB-肌酸激酶、MB-肌酸激酶和MM-肌酸激酶显著升高。褪黑素的给药通过其自由基清除机制预防了多氯联苯诱导的这些改变。因此,多氯联苯通过诱导脑区氧化应激改变肌酸激酶活性,而褪黑素可对此起到保护作用。

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