Antioxidant effects of N-acetylcysteine and succimer in red blood cells from lead-exposed rats
Antioxidant effects of N-acetylcysteine and succimer in red blood cells from lead-exposed rats
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DOI：
10.1016/s0300-483x(98)00074-2
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发表时间：
1998-07-17
期刊：
影响因子：
4.5
通讯作者：
Erçal, N
中科院分区：
文献类型：
--
作者：
Gürer, H;Özgünes, H;Erçal, N
这项研究检测了体内体内铅对红细胞(RBC)的毒性效应是否伴随着铅引起的氧化应激指标的变化。它还探索了用N-乙酰半胱氨酸(NAC)或琥珀酸(Meso-2，3-二硫代琥珀酸)处理能够逆转指示铅诱导的氧化应激的参数的可能性。Fisher 344只大鼠饮水中加入2000ppm的醋酸铅，连续5周。然后去除铅，在饮用水中给予NAC(800 mg/kg/d)或琥珀酰基异构体(90 mg/kg/d)1周，然后采集红细胞。没有给予铅的动物和给予铅的动物，而不是NAC或琥珀酸钾的动物，分别作为阴性和阳性对照。实验结束时，染铅动物的血铅水平为35+/-4mUg/dl，经琥珀酰肌醇处理后降至2.5+/-1mug/dl，经NAG处理后降至25+/-3mU/dl。暴露于铅的动物表现出贫血的迹象，表现为细胞不等、多核细胞增多，以及血红蛋白、红细胞压积和平均红细胞体积的改变。染铅大鼠红细胞脂质过氧化，表现为丙二醛(MDA)含量增加，还原型谷胱甘肽(GSH)减少，过氧化氢酶(CAT)和葡萄糖6-磷酸脱氢酶(G6PD)活性升高，提示铅诱导氧化应激。此外，血中β-氨基乙酰丙酸脱水酶(ALAD)活性的显著降低表明，β-氨基乙酰丙酸的蓄积和自氧化可能参与了铅诱导的氧化应激。NAC或琥珀酸处理逆转了铅诱导的丙二醛和谷胱甘肽含量的变化，但只有琥珀酸似乎部分恢复了ALAD活性。这些结果提供了体内证据，支持这一假说，即铅诱导红细胞氧化应激，这是可逆的处理硫醇抗氧化剂(NAC)，以及螯合剂(琥珀酸)。(C)1998爱思唯尔爱尔兰科学有限公司。保留所有权利。
This study examined whether lead-induced alterations in selected parameters that are indicative of oxidative stress accompany the toxic effects of lead in red blood cells (RBCs) in vivo. It also explored the possibility that treatment with N-acetylcysteine (NAC) or succimer (meso-2,3-dimercaptosuccinic acid) was capable of reversing parameters indicative of lead-induced oxidative stress. Fisher 344 rats were given 2000 ppm lead acetate in their drinking water for 5 weeks. The lead was then removed and the animals were given NAC (800 mg/kg/day) or succimer (90 mg/kg/day) in their drinking water for 1 week, after which the RBCs were harvested. Animals not given lead and those given lead, but not NAC or succimer, served as negative and positive controls, respectively. At the end of the experiment, blood-lead levels were 35 +/- 4 mu g/dl in lead-treated animals, which were reduced to 2.5 +/- 1 mu g/dl by treatment with succimer and to 25 +/- 3 mu g/dl by treatment with NAG. Lead-exposed animals demonstrated signs of anemia as evidenced by anisocytosis, poikilocytosis, and alterations in hemoglobin, hematocrit, and mean corpuscular volume. Lipid peroxidation, as evidenced by increased malondialdehyde (MDA) content; as well as decreases in reduced glutathione (GSH) and increases in catalase and glucose 6-phosphate dehydrogenase (G6PD) activity were noted in RBCs from lead-treated rats, suggesting that the lead induced oxidative stress. In addition, a significant reduction in blood delta-aminolevulinic acid dehydratase (ALAD) activity suggested that accumulation and autooxidation of delta-aminolevulinic acid might contribute to lead-induced oxidative stress. Treatment with either NAC or succimer reversed lead-induced alterations in MDA and GSH content, but only succimer appeared to partially restore ALAD activity. These results provide in vivo evidence supporting the hypothesis that lead induces oxidative stress in RBCs, which is reversible by treatment with a thiol antioxidant (NAC), as well as a chelating agent (succimer). (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.