Bhasker A S B, Sant Bhavana, Yadav Preeti, Agrawal Mona, Lakshmana Rao P V
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
Neurotoxicology. 2014 Sep;44:194-203. doi: 10.1016/j.neuro.2014.06.015. Epub 2014 Jul 7.
Abrin is a potent plant toxin. It is a heterodimeric protein toxin which is obtained from the seeds of Abrus precatorius plant. At cellular level abrin causes protein synthesis inhibition by removing the specific adenine residue (A4324) from the 28s rRNA of the 60S - ribosomal subunit. In the present study we investigated the role of oxidative stress in neurotoxic potential and demyelinating effects of abrin on brain. The mechanism by which abrin induces oxidative damage and toxicity in brain are relatively unknown. Animals were exposed to 0.4 and 1.0 LD50 abrin dose by intraperitoneal route and observed for 1 and 3 day post-toxin exposure. Oxidative stress occurred in brain due to abrin was confirmed in terms of increased reactive oxygen species (ROS), glutathione depletion and increased lipid peroxidation. Significant increase in blood and brain ROS was observed at day 3, 1 LD50. Abrin induced changes in the neurotransmitters (5-hydroxy tryptamine, norepinephrine, dopamine and monoamine oxidase) levels were evaluated by spectroflourometry. Increase in the levels of 5-HT and NE was observed after abrin exposure. MAO activity was found to be decreased in abrin exposed animals compared to control. Significant inhibition in the activity of acetylcholine esterase enzyme in brain and serum was reported for both the doses and time points. Western blot analysis of iNOS expression indicated that abrin treatment resulted in dose and time dependent increase. Furthermore, protein expression of myelin basic protein (MBP) was down regulated in a dose and time dependent manner. Brain histopathology was carried out and cortical brain region showed demyelination after abrin exposure. Results confirmed that abrin poisoning leads to neurodegeneration and neurotoxicity mediated through oxidative stress, AChE inhibition, lipid peroxidation and decrease in MBP levels.
相思子毒素是一种强效植物毒素。它是一种异二聚体蛋白质毒素，从相思子植物的种子中提取。在细胞水平上，相思子毒素通过从60S核糖体亚基的28S rRNA中去除特定的腺嘌呤残基（A4324）来抑制蛋白质合成。在本研究中，我们调查了氧化应激在相思子毒素对大脑的神经毒性潜力和脱髓鞘作用中的作用。相思子毒素在大脑中诱导氧化损伤和毒性的机制相对未知。通过腹腔注射途径使动物暴露于0.4和1.0 LD50剂量的相思子毒素，并在毒素暴露后1天和3天进行观察。根据活性氧（ROS）增加、谷胱甘肽消耗和脂质过氧化增加，证实了相思子毒素导致大脑中的氧化应激。在第3天，观察到1 LD50剂量时血液和大脑中的ROS显著增加。通过荧光光谱法评估相思子毒素诱导的神经递质（5-羟色胺、去甲肾上腺素、多巴胺和单胺氧化酶）水平变化。相思子毒素暴露后观察到5-HT和NE水平升高。与对照组相比，发现相思子毒素暴露动物的MAO活性降低。对于两种剂量和时间点，均报告大脑和血清中的乙酰胆碱酯酶活性受到显著抑制。iNOS表达的蛋白质印迹分析表明，相思子毒素处理导致剂量和时间依赖性增加。此外，髓鞘碱性蛋白（MBP）的蛋白质表达以剂量和时间依赖性方式下调。进行了大脑组织病理学检查，发现相思子毒素暴露后大脑皮质区域出现脱髓鞘。结果证实，相思子毒素中毒导致神经退行性变和神经毒性，其介导机制包括氧化应激、乙酰胆碱酯酶抑制、脂质过氧化和MBP水平降低。
