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在伤寒沙门氏菌脂多糖全身和局部给药的情况下,槲皮素增强了表没食子儿茶素-3-没食子酸酯在大鼠牙周组织中的抗自由基特性。

Quercetin potentiates antiradical properties of epigallocatechin-3-gallate in periodontium of rats under systemic and local administration of lipopolisaccharide of salmonella typhi.

作者信息

Yelins’ka Alina M., Liashenko Lilia I, Kostenko Vitalii O

机构信息

Ukrainian Medical Stomatological Academy, Poltava, Ukraine

出版信息

Wiad Lek. 2019 Aug 31;72(8):1499-1503.

PMID:32012499
Abstract

INTRODUCTION

There has been demonstrated that pharmaceutical effect of epigallocatechin-3-gallate (EGCG), a polyphenol, which is found in green tea (Camellia sinensis), is implemented through the activation of Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2).The importance of Keap1 / Nrf2 / antioxidant response element (ARE) system is determined by the fact that the state of NF-κB- and АР-1-associated pathways depends on its activity. Recent studies have demonstrated the property of quercetin to suppress ubiquitin-dependent proteolysis of complex of NF-κB and its inhibitory protein IκB. All this provides preconditions to eliminate the potentiality of NF-κB-dependent expression of the number of genes of pro-oxidant and pro-inflammatory proteins. However, co-effect produced by quercetin and EGCG on the oxidative nitrosative stress markers in the periodontal tissues is still unclear.

THE AIM

To investigate the co-effect produced by quercetin and an inducer of the Keap1 / Nrf2 / ARE epigallocatechin-3-gallate on markers of oxidative-nitrosative stress in rats’ periodontium under the systemic and local administration of Salmonella typhi lipopolysaccharide (LPS).

MATERIAL AND METHODS

The studies were conducted on 30 white rats of the Wistar line, divided into 5 groups: the 1st included intact animals, the 2nd was made up of animals after their exposure to combined systemic and local LPS administration, the 3rd and 4th groups included animals, which were given injections with water-soluble form of quercetin (corvitin) and EGCG respectively, and the 5th group involved rats, which were injected with co-administered corvitin and EGCG. The formation of superoxide anion radical (.О-2 ) was evaluated by a test with nitro blue tetrazolium using spectrophotometry of the periodontal soft tissue homogenate. The total activity of NO-synthase and concentration of peroxynitrite in the homogenate of the soft components of periodontium were evaluated spectrophotometrically.

RESULTS

Co-effect produced by corvitin and EGCG under systemic and local LPS administration is accompanied with reduced О-2 production by NADPH-dependent electron transport chains (microsomal and NOS) by 20.0 % (p <0.05) compared with values for the animals received separate corvitin during the experiment. .О-2 generation by the mitochondrial respiratory chain yielded to comparable data of the 3rd and 4th groups by 27.6 % (p <0.01) and 23.8 % (p <0.05) respectively. No differences were found between the groups exposed to combined or separate action of the above mentioned agents in the experiment when assessing О-2 generation by leukocyte NADPH-oxidase. Combined effect of corvitin and EGCG during systemic and local LSP administration showed the decrease in NOS activity and peroxynitrite concentration in periodontal tissues by 53.3 % (p <0.001) and 27.0 % (p <0.02) compared with the findings in the 3rd group, and by 42.0 % (p <0.01) and 22.3 % (p <0.01) in the 4th group.

CONCLUSIONS

The co-administration of water-soluble form of quercetin and epigallocatechin-3-gallate under systemic and local introducing of lipopolysaccharide Salmonella typhi has been proven to be more effective means for preventing and correcting oxidative-nitrosative stress in the periodontal tissues than this occurs at separate administration of each of the polyphenols.

摘要

引言

已证实绿茶(茶树)中含有的多酚表没食子儿茶素没食子酸酯(EGCG)的药理作用是通过激活核因子E2相关因子2(Nrf2)实现的。Keap1 / Nrf2 /抗氧化反应元件(ARE)系统的重要性在于,NF-κB和AP-1相关信号通路的状态取决于其活性。最近的研究表明,槲皮素具有抑制NF-κB及其抑制蛋白IκB复合物的泛素依赖性蛋白水解的特性。所有这些为消除促氧化剂和促炎蛋白的多个基因的NF-κB依赖性表达的可能性提供了前提条件。然而,槲皮素和EGCG对牙周组织中氧化亚硝化应激标志物的联合作用仍不清楚。

目的

研究槲皮素和Keap1 / Nrf2 / ARE表没食子儿茶素没食子酸酯诱导剂在伤寒沙门氏菌脂多糖(LPS)全身和局部给药下对大鼠牙周组织氧化亚硝化应激标志物的联合作用。

材料与方法

对30只Wistar系白色大鼠进行研究,分为5组:第1组为未处理动物;第2组由全身和局部联合给予LPS后的动物组成;第3组和第4组分别为注射水溶性槲皮素(柯维丁)和EGCG的动物;第5组为同时注射柯维丁和EGCG的大鼠。使用分光光度法对牙周软组织匀浆进行硝基蓝四唑试验,评估超氧阴离子自由基(·О-2)的形成。采用分光光度法评估牙周组织软成分匀浆中一氧化氮合酶的总活性和过氧亚硝酸盐的浓度。

结果

与实验中单独接受柯维丁的动物相比,在全身和局部给予LPS的情况下,柯维丁和EGCG的联合作用使NADPH依赖性电子传递链(微粒体和NOS)产生的О-2减少了20.0%(p<0.05)。线粒体呼吸链产生的·О-2分别比第3组和第4组的可比数据降低了27.6%(p<0.01)和23.8%(p<0.05)。在评估白细胞NADPH氧化酶产生的·О-2时,实验中联合或单独使用上述药物的组之间未发现差异。在全身和局部给予LSP的情况下,柯维丁和EGCG的联合作用使牙周组织中NOS活性和过氧亚硝酸盐浓度分别比第3组降低了53.3%(p<0.001)和27.0%(p<0.02),比第4组降低了42.0%(p<0.01)和22.3%(p<0.01)。

结论

已证明在全身和局部引入伤寒沙门氏菌脂多糖的情况下,联合给予水溶性槲皮素和表没食子儿茶素没食子酸酯比单独给予每种多酚更有效地预防和纠正牙周组织中的氧化亚硝化应激。

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