Acute toxicity of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) in male Sprague-Dawley rats: effects on hepatic oxidative stress, glutathione and metals status.
Acute toxicity of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) in male Sprague-Dawley rats: effects on hepatic oxidative stress, glutathione and metals status.
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DOI：
10.1016/j.envint.2009.11.002
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发表时间：
2010-11
影响因子：
11.8
通讯作者：
Robertson, Larry W.
中科院分区：
文献类型：
--
作者：
Lai, Ian;Chai, Yingtao;Simmons, Don;Luthe, Gregor;Coleman, Mitchell C.;Spitz, Douglas;Haschek, Wanda M.;Ludewig, Gabriele;Robertson, Larry W.
尽管美国在 20 世纪 70 年代停止了多氯联苯 (PCB) 的生产和 PCB 的新用途，但 PCB 仍继续在封闭系统中使用，并持续存在于环境中，在脂肪组织中积累。 PCB 是药物代谢的有效诱导剂，可能会增加氧化事件并改变细胞和组织内的许多其他生化和形态参数。本研究的目的是评估单一、极低剂量的 PCB 126（3,3',4,4',5-五氯联苯）（一种共面的二恶英类 PCB 同系物和芳烃受体 (AhR) 激动剂）对氧化还原状态、金属稳态、抗氧化酶和细胞形态的影响。为了检查这些参数，给雄性 Sprague-Dawley 大鼠喂食含有 0.2 ppm 硒的纯化 AIN-93 基础饮食两周，然后进行单次腹膜内注射。注射玉米油（5ml/kg体重）或玉米油中的1μmol PCB 126/kg体重（326μg/kg体重）。在对大鼠实施安乐死之前，将大鼠继续保持这种饮食两周。该剂量的 PCB 126 不会延迟采食量或生长，但会显着增加肝脏重量 (42%) 和肝微粒体细胞色素 P-450 (CYP1A) 酶活性（增加 10-40 倍）。 PCB 126 使肝锌、硒和谷胱甘肽水平分别显着降低 15%、30% 和 20%。这些变化伴随着硒依赖性谷胱甘肽过氧化物酶活性降低 25%。相比之下，PCB 126 使肝铜水平增加 40%。PCB 126 诱导的病理学特征为肝细胞肥大和肝脏轻度脂肪变性以及胸腺皮质 T 细胞轻度减少。这项对喂食纯化饮食的大鼠进行的对照研究表明，即使是单一、极低剂量的 PCB 126 不会改变饲料摄入量或生长，也会显着扰乱啮齿动物肝脏中的氧化还原和金属稳态以及抗氧化剂和酶水平。
Although polychlorinated biphenyl (PCBs) production, and new uses for PCBs, was halted in the 1970s in the United States, PCBs continue to be used in closed systems and persist in the environment, accumulating in fatty tissues. PCBs are efficacious inducers of drug metabolism and may increase oxidative events and alter many other biochemical and morphologic parameters within cells and tissues. The goal of the present study was to evaluate the effects of a single, very low dose of PCB 126 (3,3′,4,4′,5-pentachlorobiphenyl), a coplanar, dioxin-like PCB congener and aryl hydrocarbon receptor (AhR) agonist, on the redox status, metals homeostasis, antioxidant enzymes, and cellular morphology. To examine these parameters, male Sprague-Dawley rats were fed a purified AIN-93 basal diet containing 0.2 ppm selenium for two weeks, then administered a single i.p. injection of corn oil (5 ml/kg body weight) or 1 μmol PCB 126/kg body weight (326 μg/kg body weight) in corn oil. Rats were maintained on the diet for an additional two weeks before being euthanized. This dose of PCB 126 did not later feed intake or growth, but significantly increased liver weight (42%) and hepatic microsomal cytochrome P-450 (CYP1A) enzyme activities (10–40-fold increase). Hepatic zinc, selenium, and glutathione levels were significantly decreased 15%, 30%, and 20%, respectively, by PCB 126. These changes were accompanied by a 25% decrease in selenium-dependent glutathione peroxidase activity. In contrast, hepatic copper levels were increased 40% by PCB 126. PCB 126-induced pathology was characterized by hepatocellular hypertrophy and mild steatosis in the liver and a mild decrease in cortical T-cells in the thymus. This controlled study in rats fed a purified diet shows that even a single, very low dose of PCB 126 that did not alter feed intake or growth, significantly perturbed redox and metals homeostasis and antioxidant and enzyme levels in rodent liver.
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影响因子：
5.1
作者：
BANDIERA, S;SAFE, S;OKEY, AB
通讯作者：
OKEY, AB
DOI：
10.1016/0006-291x(76)90747-6
发表时间：
1976-01-01
影响因子：
3.1
作者：
LAWRENCE, RA;BURK, RF
通讯作者：
BURK, RF
影响因子：
2.9
作者：
GRIFFITH, OW
通讯作者：
GRIFFITH, OW
影响因子：
4.2
作者：
CHEN, LC;BORGES, T;ROBERTSON, LW
通讯作者：
ROBERTSON, LW
影响因子：
3.8
作者：
Fisher, JW;Campbell, J;Almekinder, TL
通讯作者：
Almekinder, TL