肝保护剂对酒精性肝炎患者血液氧化稳态影响的比较评价:一项随机实验研究

I. Bykov, G. Ermakova, K. Popov, I. Tsymbalyuk, M. I. Bykov, Y. E. Denisova, S. M. Tutarisheva
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引用次数: 0

摘要

背景对已发表的护肝剂的化学结构、药效学和药代动力学及其实际应用的分析表明,对护肝剂药理学的全面认识尚待发展。因此,抗氧化活性与减少肝细胞溶解的有效性之间的关系尚不清楚。另一个难题涉及肝保护剂的应用适应症、特定药物的选择和治疗持续时间。目标。探讨不同作用机制的肝保护剂对酒精性肝炎患者血液氧化代谢指标的影响。方法。四组患者参与了这项研究。第一组为相对健康的男性患者(n=15)。其余组(每组10人)由中度酒精性肝炎患者代表。第2组患者接受remaxol;第3组患者接受腺苷;第4组患者接受熊去氧胆酸治疗。在治疗前后,测定血液中细胞溶解和氧化应激的指标。使用StatPlus v 7(AnalystSoft股份有限公司)软件包进行统计数据处理。后果根据观察到的溶细胞综合征标志酶的变化,研究中的所有三种护肝剂都表现出相当的疗效。根据任何应用方案治疗后,血浆中的ALT和AST活性与初始值相比分别下降了56-68%和75-81%。与对照组相比,血浆总抗氧化活性下降了20-27%;红细胞悬浮液中TBA反应产物的含量增加了61–87%。残余醇、阿替甲硫氨酸或熊去氧胆酸治疗导致上述参数的部分正常化,而实验组之间没有显著差异。与对照组相比,患者红细胞悬浮液中还原型谷胱甘肽的浓度和血浆中巯基的含量分别降低了16%和26%。治疗后,这些指标也增加了12-15%,尽管研究的任何一种护肝剂都没有显示出主要作用。结论所进行的比较研究表明,在remaxol、腺嘌呤甲硫氨酸和熊去氧胆酸的药理作用机制中,没有特定的抗氧化作用。在这方面,应该进行进一步的研究,以研究护肝药物对病理生化变化的影响,并分析抗氧化作用与降低肝细胞裂解水平的疗效之间的关系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comparative Evaluation of the Effect of Hepatoprotectors on Oxidative Homeostasis in the Blood of Patients with Alcoholic Hepatitis: A Randomized Experimental Study
Background. An analysis of published results on the chemical structure, pharmacodynamics and pharmacokinetics of hepatoprotective agents, as well as their practical application, shows that a holistic view on the pharmacology of hepatoprotective agents is yet to be developed. Thus, the relationship between antioxidant activity and the effectiveness of reducing hepatocyte cytolysis remains unclear. Another difficult question concerns indications for the application of hepatoprotectors, selection of a particular drug and treatment duration.Objectives. To investigate the effects of hepatoprotective agents with different mechanisms of action on the indicators of oxidative metabolism in the blood of patients with alcoholic hepatitis.Methods. Four groups of patients were involved in the study. The 1st group consisted of relatively healthy male patients (n = 15). The remaining groups (10 individuals in each) were represented by patients with moderate alcoholic hepatitis. Patients of the 2nd group received remaxol; patients of the 3rd group received ademetionine; patients of the 4th group received ursodeoxycholic acid. Prior to and following treatment, the indicators of cytolysis and oxidative stress in blood were determined. Statistical data processing was carried out using the StatPlus v 7 (AnalystSoft Inc.) software package.Results. According to the observed changes in the cytolytic syndrome marker enzymes, all three hepatoprotectors under study expressed comparable efficacy. After treatment according to any of the applied schemes, the ALT and AST activity in the blood plasma decreased by 56–68% and 75–81%, respectively, compared to their initial values. In comparison with the control group, the total antioxidant activity of the blood plasma decreased by 20–27%; the content of TBA-reactive products in the erythrocyte suspension increased by 61–87%. The remaxol, ademethionine or ursodeoxycholic acid therapy led to a partial normalization of the abovementioned parameters without significant differences between the experimental groups. The concentration of reduced glutathione in the erythrocyte suspension and the content of thiol groups in the blood plasma of patients were reduced in comparison with the control group by 16% and 26%, respectively. After therapy, these indicators also increased by 12–15%, although no predominant effect of either of the studied hepatoprotectors was revealed.Conclusion. The conducted comparative study indicated the absence of a specific antioxidant effect among the pharmacological mechanisms of action of remaxol, ademethionine and ursodeoxycholic acid. In this regard, further research should be carried out to investigate the effect of hepatoprotective drugs on pathobiochemical changes and to analyse a relationship between the antioxidant effect and the efficacy of reducing the level of hepatocyte cytolysis.
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