6-Hydroxy-2,2,4-trimethyl-1,2-diHydrquinoline 在对乙酰氨基酚引起的大鼠肝损伤中具有抗炎特性并减少氧化应激。,Current Issues in Molecular Biology

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6-Hydroxy-2,2,4-trimethyl-1,2-diHydrquinoline 在对乙酰氨基酚引起的大鼠肝损伤中具有抗炎特性并减少氧化应激。
Current Issues in Molecular Biology ( IF 2.8 ) Pub Date : 2023-10-12 , DOI: 10.3390/cimb45100525
Evgenii D Kryl'skii ₁ , Svetlana E Kravtsova ₁ , Tatyana N Popova ₁ , Larisa V Matasova ₁ , Khidmet S Shikhaliev ₂ , Svetlana M Medvedeva ₂

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我们研究了 6-羟基-2,2,4-三甲基-1,2-二氢喹啉对对乙酰氨基酚诱导的肝损伤大鼠的肝损伤标志物、氧化状态以及炎症和细胞凋亡过程的程度的影响。对乙酰氨基酚的给药引起8-羟基-2-脱氧鸟苷和8-异前列腺素在肝脏和血清中的积累，以及生化发光指标的增加。氧化应激导致促炎细胞因子和 NF-κB 因子 mRNA 合成的激活，免疫球蛋白 G 水平的增加，以及 caspase-3、caspase-8 和 caspase-9 活性的升高。使用对乙酰氨基酚还会导致氧化应激的发生，导致还原型谷胱甘肽水平下降和抗氧化酶功能失衡。这项研究发现，6-羟基-2,2,4-三甲基-1,2-二氢喹啉通过其抗氧化活性减少氧化应激，从而降低促炎细胞因子和 NF-κB mRNA 的水平，并降低浓度这些变化导致 caspase-8 和 caspase-9 活性降低，它们参与配体诱导的凋亡途径和线粒体途径的激活，并抑制效应器 caspase-3。此外，6-羟基-2,2,4-三甲基-1,2-二氢喹啉促进了接受对乙酰氨基酚治疗的动物抗氧化系统功能的正常化。结果，正在测试的化合物通过减少氧化应激减轻炎症和细胞凋亡，从而改善肝脏标志物指数并改善组织病理学改变。

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6-Hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline Demonstrates Anti-Inflammatory Properties and Reduces Oxidative Stress in Acetaminophen-Induced Liver Injury in Rats.

We examined the effects of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on markers of liver injury, oxidative status, and the extent of inflammatory and apoptotic processes in rats with acetaminophen-induced liver damage. The administration of acetaminophen caused the accumulation of 8-hydroxy-2-deoxyguanosine and 8-isoprostane in the liver and serum, as well as an increase in biochemiluminescence indicators. Oxidative stress resulted in the activation of pro-inflammatory cytokine and NF-κB factor mRNA synthesis and increased levels of immunoglobulin G, along with higher activities of caspase-3, caspase-8, and caspase-9. The administration of acetaminophen also resulted in the development of oxidative stress, leading to a decrease in the level of reduced glutathione and an imbalance in the function of antioxidant enzymes. This study discovered that 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline reduced oxidative stress by its antioxidant activity, hence reducing the level of pro-inflammatory cytokine and NF-κB mRNA, as well as decreasing the concentration of immunoglobulin G. These changes resulted in a reduction in the activity of caspase-8 and caspase-9, which are involved in the activation of ligand-induced and mitochondrial pathways of apoptosis and inhibited the effector caspase-3. In addition, 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline promoted the normalization of antioxidant system function in animals treated with acetaminophen. As a result, the compound being tested alleviated inflammation and apoptosis by decreasing oxidative stress, which led to improved liver marker indices and ameliorated histopathological alterations.

更新日期：2023-10-12

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