新出现的痕量农药污染物扰乱了小鼠不同器官中的生物大分子:过氧化物酶体增殖激活受体-α的作用

Pavani K. Gonnabathula, M. Yakubu
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引用次数: 0

摘要

关于长期接触环境相关(痕量浓度)的新兴污染物对生物大分子的影响,目前还缺乏相关信息。这些化学混合物在环境中的暴露是以痕量浓度和多种分子相互作用的方式发生的。研究人员调查了痕量浓度的多种杀虫剂(MPs)对野生型(WT)和基因缺陷型过氧化物酶体增殖激活受体-α(PPARα)基因敲除(Null)小鼠组织中特定生物大分子一氧化氮(NO)、硫醇、超氧化物歧化酶(SOD)和谷胱甘肽 S-转移酶(GST)的调节作用。小鼠在饮用水中接触痕量浓度的 MPs:阿特拉津、狄氏剂、异狄氏剂、硫丹和蒽(1-100 ng/L),为期 6 周。在 WT 和 PPARα 基因敲除组中观察到了不同处理对器官的选择性影响。在 WT 和 PPARα 基因敲除者的器官中观察到了 NO 水平的增加,而肾脏(Null)的增加有限。与对照组相比,WT 的器官中 SOD 活性降低,而 PPARα 基因敲除者的 SOD 活性升高。与对照组相比,WT 小鼠心脏和脾脏中的硫醇含量明显增加,PPARα 基因敲除小鼠心脏中的硫醇含量也明显增加。与对照组相比,WT 小鼠心脏和肾脏中的非蛋白质硫醇浓度降低,而 PPARα 基因敲除小鼠肝脏中的非蛋白质硫醇浓度降低。与 WT 相比,肝脏和脾脏(WT)中的 GST 活性明显降低,而 PPARα 基因敲除小鼠所有器官中的 GST 活性都明显升高。观察到的这些效应可能会受到遗传状况的影响,如 PPARα 缺乏症。这些结果表明,纳米富集的一系列有机污染物可导致生物大分子的细胞和分子失调,从而产生毒性和病理变化,对人类健康构成威胁。有必要进一步研究这些失调所涉及的分子机制和信号通路。
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Emerging contaminants at trace levels of pesticides perturbs biomolecules in different organs in mice: Role of peroxisome proliferator-activated receptor-alpha
Information is lacking on the consequences of chronic exposure to emerging contaminants at environmentally relevant (trace concentrations) on biomolecules. Environmental exposure to these chemical mixtures happens at trace concentrations and at multiple molecular interactions. The consequences of trace concentrations of multiple pesticides (MPs) on the regulation of selected biomolecules nitric oxide (NO), thiols, superoxide dismutase (SOD), and glutathione S-transferase (GST) in the tissues from wild type (WT) and genetically deficient- peroxisome proliferator-activated receptor-alpha (PPARα) knockout (Null) mice were investigated. Mice were exposed to trace concentrations of MPs: Atrazine, dieldrin, endrin, endosulfan, and anthracene (1–100 ng/L) in drinking water for 6 weeks. Organs were collected and homogenized; NO, protein and non-protein thiol levels, as well as SOD and GST activities were determined. Differential and organ selective effects of the treatments were observed in the WT and PPARα knockout. Increased NO levels were observed in the organs from WT with limited increase in the kidney (Null). SOD activity was decreased in the organs from the WT and was increased in the PPARα knockout when compared to the control. Thiol level was significantly increased in the heart and spleen in the WT and in the heart of the PPARα knockout mice when compared to the control. Non-protein thiol concentration was reduced in the heart and kidney (WT) and reduced in the liver of the PPARα knockout when compared to the control. GST activity was significantly decreased in the liver and spleen (WT) and was significantly elevated in all organs in the PPARα knockout mice when compared to the WT. The low concentrations of MPs may have caused selective dysregulation of biomolecules in different organs of the body. These effects observed may be influenced by genetic status such as in PPARα deficiency. These results present a scenario that implicates nanoconcentrations of series of organic contaminants that can cause cellular and molecular dysregulations of biomolecules precipitating toxicity and pathology that can be a threat to human health. Further, investigation into the molecular mechanism(s) and signaling pathway(s) implicated in these dysregulations is warranted.
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