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Ion Imbalance Is Involved in the Mechanisms of Liver Oxidative Damage in Rats Exposed to Glyphosate

机译:草甘膦暴露于大鼠肝脏氧化损伤的机制涉及离子失衡

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摘要

Glyphosate (N-phosphonomethyl-glycine, GLP) is the most popular herbicide used worldwide. This study aimed to investigate the effects of glyphosate on rats' liver function and induction of pathological changes in ion levels and oxidative stress in hepatic tissue. Sprague-Dawley rats were treated orally with 0, 5, 50, and 500 mg/kg body weight of the GLP. After 5 weeks of treatment, blood and liver samples were analyzed for biochemical and histomorphological parameters. The various mineral elements content in the organs of the rats were also measured. Significant decreases were shown in the weights of body, liver, kidney and spleen between the control and treatment groups. Changes also happened in the histomorphology of the liver and kidney tissue of GLP-treated rats. The GLP resulted in an elevated level of glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and IL-1β in the serum. Besides, decreased total superoxide dismutase (T-SOD) activity and increased malondialdehyde (MDA) contents in the serum, liver, and kidney indicated the presence of oxidative stress. Moreover, increase of hydrogen peroxide (H2O2) level and catalase (CAT) activity in the serum and liver and decrease of glutathione (GSH) and lutathione peroxidase (GSH-Px) activity in the kidney tissue further confirmed the occurrence of oxidative stress. The results of RT-PCR showed that the mRNA expressions of IL-1α, IL-1β, IL-6, MAPK3, NF-κB, SIRT1, TNF-α, Keap1, GPX2, and Caspase-3 were significantly increased in the GLP-treated groups compared to the control group. Furthermore, PPARα, DGAT, SREBP1c, and SCD1 mRNA expressions were also remarkably increased in the GLP-treated groups compared to the control group. In addition, aluminum (Al), iron (Fe), copper (Cu), zinc (Zn), and magnesium (Mg) levels were showed a significant difference reduction or increase in rat liver, kidney, spleen, lung, heart, muscle, brain, and fat tissues. These results suggested that glyphosate caused obvious damage to rats' liver and caused various mineral elements content imbalances in various organs of rats. Ion imbalance could weaken antioxidant capacity and involve in the mechanism of liver oxidative damage caused by GLP.
机译:草甘膦(N-膦酰基甲基甘氨酸,GLP)是世界上使用最广泛的除草剂。本研究旨在探讨草甘膦对大鼠肝功能的影响以及诱导肝脏组织中离子水平和氧化应激的病理变化。对Sprague-Dawley大鼠进行口服,0、5、50和500 mg / kg的GLP体重治疗。治疗5周后,分析了血液和肝脏样品的生化和组织形态学参数。还测量了大鼠器官中各种矿物质元素的含量。对照组和治疗组之间的身体,肝脏,肾脏和脾脏的重量明显减少。 GLP治疗的大鼠的肝脏和肾脏组织的组织形态也发生了变化。 GLP导致血清中谷氨酸-草酰乙酸转氨酶(GOT),谷氨酸-丙酮酸转氨酶(GPT)和IL-1β升高。此外,血清,肝脏和肾脏中总超氧化物歧化酶(T-SOD)活性降低和丙二醛(MDA)含量增加表明存在氧化应激。此外,血清和肝脏中过氧化氢(H2O2)水平和过氧化氢酶(CAT)活性的增加以及肾脏组织中谷胱甘肽(GSH)和硫代过氧化物酶(GSH-Px)活性的降低进一步证实了氧化应激的发生。 RT-PCR结果显示,GLP中IL-1α,IL-1β,IL-6,MAPK3,NF-κB,SIRT1,TNF-α,Keap1,GPX2和Caspase-3的mRNA表达显着增加。治疗组与对照组比较。此外,与对照组相比,GLP治疗组的PPARα,DGAT,SREBP1c和SCD1 mRNA表达也显着增加。此外,铝(Al),铁(Fe),铜(Cu),锌(Zn)和镁(Mg)的含量在大鼠肝脏,肾脏,脾脏,肺,心脏,肌肉中显示出明显的减少或增加的差异。 ,大脑和脂肪组织。这些结果表明草甘膦对大鼠肝脏有明显的损害,并导致大鼠各个器官中各种矿物质元素的含量失衡。离子失衡会削弱抗氧化能力,并参与GLP引起的肝氧化损伤机制。

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