Citric Acid Effects on Brain and Liver Oxidative Stress in Lipopolysaccharide-Treated Mice
Citric Acid Effects on Brain and Liver Oxidative Stress in Lipopolysaccharide-Treated Mice
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DOI：
10.1089/jmf.2013.0065
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发表时间：
2014-05-01
影响因子：
2.4
通讯作者：
Sleem, Amany A.
中科院分区：
文献类型：
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作者：
Abdel-Salam, Omar M. E.;Youness, Eman R.;Sleem, Amany A.
柠檬酸是一种弱有机酸，在柑橘类水果中含量最高。本研究检测了柠檬酸对内毒素诱导的脑和肝氧化应激的影响。用单次腹膜内剂量的脂多糖（LPS; 200 μ g/kg）攻击小鼠。在注射内毒素时以1、2或4g/kg经口给予柠檬酸，并在4 h后对小鼠实施安乐死。LPS诱导脑和肝组织的氧化应激，导致脂质过氧化（丙二醛[MDA]）和亚硝酸盐的显着增加，而显着降低还原型谷胱甘肽，谷胱甘肽过氧化物酶（GPx），对氧磷酶1（PON 1）的活性。内毒素注射后，脑组织中肿瘤坏死因子-α（TNF-α）明显增加。柠檬酸（1-2g/kg）的给药减轻了LPS诱导的脑MDA、亚硝酸盐、TNF-α、GPx和PON 1活性的升高。在肝脏中，1g/kg柠檬酸可降低亚硝酸盐。柠檬酸使GPx活性升高，而PON 1活性降低。1-2g/kg柠檬酸可减轻LPS诱导的肝损伤、DNA片段化、血清转氨酶升高、caspase-3和诱导型一氧化氮合酶表达。然而，在4g/kg柠檬酸后，DNA片段化增加。因此，在该全身性炎症模型中，柠檬酸（1-2g/kg）可降低脑脂质过氧化和炎症、肝损伤和DNA片段化。
Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 g/kg). Citric acid was given orally at 1, 2, or 4g/kg at time of endotoxin injection and mice were euthanized 4h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1-2g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-, GPx, and PON1 activity. In the liver, nitrite was decreased by 1g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1-2g/kg citric acid. DNA fragmentation, however, increased after 4g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1-2g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.