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Hepatoprotective and Antioxidant Activity of 8,8-Dimethyl-5-P-Tolyl-3,4,7,8-Tetrahydro-2 H -Pyrido[4,3,2- de ]Cinnolin-3-One
Pharmaceutical Chemistry Journal ( IF 0.9 ) Pub Date : 2020-11-19 , DOI: 10.1007/s11094-020-02272-1
S. S. Zykova , S. N. Shurov , I. A. Rodin , A. G. Koshchaev , M. S. Danchuk , A. P. Chernobrovkina , K. V. Bezmaternykh , G. V. Smirnova , O. N. Oktyabr’skii , M. A. Kokhanov

The hepatoprotective activity of 8,8-dimethyl-5-p-tolyl-3,4,7,8-tetrahydro-2H-pyrido[4,3,2-de]cinnolin-3-one was studied in vivo using a model of CCl4-induced acute toxic hepatitis. It was found that this compound affected indices determining the level of free-radical oxidation, i.e., levels of malondialdehyde (MDA) and diene conjugates (DC), and the activities of the key antioxidant enzymes superoxide dismutase (SOD) and catalase. Hepatoprotective activity was analyzed using the activity levels of the enzymes alanine aminotransferase (AlAT), aspartate aminotransferase (AsAT), and alkaline phosphatase and the bilirubin level. The mechanism of the antioxidant activity was determined from the effect of this compound on the expression levels of the gene katG encoding catalase-hydroperoxidase I and the gene sodA encoding Mn-superoxide dismutase. It was found that 8,8-dimethyl-5-p-tolyl-3,4,7,8-tetrahydro-2H-pyrido[4,3,2-de]-cinnolin-3-one exhibited antioxidant activity by increasing the SOD and catalase levels.



中文翻译:

8,8-二甲基-5-P-甲苯基-3,4,7,8-四氢-2 H-吡啶基[4,3,2-de]肉桂醇-3-一的保肝和抗氧化活性

8,8-二甲基-5-的保肝活性p -甲苯基-3,4,7,8-四氢-2 ħ吡啶并[4,3,2- DE ]噌啉-3-酮,研究在体内使用CCl 4模型引起的急性中毒性肝炎。发现该化合物影响确定自由基氧化水平的指数,即丙二醛(MDA)和二烯共轭物(DC)的水平,以及关键的抗氧化酶超氧化物歧化酶(SOD)和过氧化氢酶的活性。使用丙氨酸转氨酶(AlAT),天冬氨酸转氨酶(AsAT)和碱性磷酸酶的活性水平以及胆红素水平分析了肝保护活性。根据该化合物对编码过氧化氢酶-过氧化氢酶I的katG基因和编码Mn-超氧化物歧化酶的sodA的表达水平的影响,确定抗氧化剂活性的机制。发现8,8-二甲基-5-甲苯基-3,4,7,8-四氢-2H-吡啶并[4,3,2- de ] -cinnolin-3-one通过增加SOD和过氧化氢酶水平表现出抗氧化活性。

更新日期:2020-11-19
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