The involvement of nitric oxide in maneb- and paraquat-induced oxidative stress in rat polymorphonuclear leukocytes
The involvement of nitric oxide in maneb- and paraquat-induced oxidative stress in rat polymorphonuclear leukocytes
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DOI：
10.1080/10715760802513733
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Singh, Chetna
中科院分区：
文献类型：
--
作者：
Ahmad, Israr;Kumar, Ashutosh;Singh, Chetna
氧化应激在代森锰（MB）和百草枯（PQ）诱导的毒性（包括MB+ PQ诱导的帕金森病（PD））的表现中起着至关重要的作用。多形核白细胞（polymorphisms leukocytes，PMNs）积极参与氧化应激介导的炎症反应和器官毒性。本研究旨在探讨MB和/或PQ诱导的大鼠中性粒细胞氧化应激指标的改变。动物以暴露时间依赖性方式接受或不接受MB和/或PQ处理。在一些实验组中，用NOS抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）和氨基胍（AG）与相应的对照沿着预处理动物。髓过氧化物酶（MPO），超氧化物歧化酶（SOD），一氧化氮，诱导型一氧化氮合酶的表达和脂质过氧化反应（LPO）的MB和/或PQ处理的动物的中性粒细胞中观察到显着增加，而过氧化氢酶和谷胱甘肽S-转移酶（GST）的活动减弱。L-NAME和AG可显著降低MB和PQ暴露动物体内升高的亚硝酸盐含量、iNOS表达和MPO活性。虽然L-NAME和AG处理的大鼠PMNs中增加的LPO也显著降低，但与对照组相比，其水平仍然较高。NOS抑制剂不影响SOD和GST活性的变化。因此，结果表明，MB和/或PQ诱导iNOS介导的一氧化氮产生，这反过来又增加MPO活性和脂质过氧化，从而氧化应激。
Oxidative stress plays a crucial role in the manifestations of maneb (MB) and paraquat (PQ)-induced toxicity including MB+PQ-induced Parkinson's disease (PD). Polymorphonuclear leukocytes (PMNs) actively participate in the oxidative stress-mediated inflammation and organ toxicity. The present study was undertaken to investigate the MB- and/or PQ-induced alterations in the indices of oxidative stress in rat PMNs. Animals were treated with or without MB and/or PQ in an exposure time dependent manner. In some sets of experiments, the animals were pre-treated with NOS inhibitors NG-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG) along with respective controls. A significant increase in myeloperoxidase (MPO), superoxide dismutase (SOD), nitric oxide, iNOS expression and lipid peroxidation (LPO) was observed in PMNs of MB- and/or PQ-treated animals, while catalase and glutathione S-transferase (GST) activities were attenuated. L-NAME and AG significantly reduced the augmented nitrite content, iNOS expression and MPO activity to control level in MB and PQ exposed animals. Although the augmented LPO was also reduced significantly in L-NAME and AG treated rat PMNs, the level was still higher as compared with controls. Alterations induced in SOD and GST activities were not affected by NOS inhibitors. The results thus suggest that MB and/or PQ induce iNOS-mediated nitric oxide production, which in turn increases MPO activity and lipid peroxidation, thereby oxidative stress.