The effect of modern hepatotoxicants on the elimination of caffeine

O. Popova, V. S. Ponamarev, A. Kostrova, L. Agafonova
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Abstract

Hepatotoxicants are a variety of chemical substances that can have organ-specific damaging  effects,  which  may  be  the  result  of their direct effects on both hepatocytes and other structural units of the liver. The purpose of this study is to evaluate the effect of modern hepatotoxicants on caffeine elimination. The studies were carried out in the vivarium of the Department of Pharmacology and Toxicology of the Federal State Budgetary Educational Institution of Higher Education  of  St.  Petersburg  State  University  of Medicine. Industrial substances of different chemical  groups  have  been  used  to  induce hepatotoxic  conditions:  phthalic  anhydride, ethylenediamine and chloroform. All of the above  toxicants  were  given  in  dosages  for the immediate (within 24 hours) induction of hepatotoxic  conditions.  One  day  after  the completion  of  the  simulation,  the  levels  of caffeine  in  the  blood  serum  of  the  experimental animals were determined in full accordance with the previous series of experiments, using a dosage of 100 mg/kg, since with this dosage regimen  we identified  the most stable pharmacokinetic profiles of caffeine.  Mathematical  and  statistical  processing of the obtained data was carried out using  the  STATISTICA  6.1  program.  The arithmetic mean (M) and its mean error (m) were calculated; the significance of the difference (p) was not calculated using the Student's test due to the  exploratory nature of the study and the lack of comparison groups. Based  on  the  conducted  research,  we  can conclude that each hepatotoxicant has individual  characteristic  characteristics,  which allows us to recommend a caffeine test for different types of hepatotoxicity, incl. unexpressed. That is, in this way it is possible to diagnose  hepatotoxic  conditions  even  in  a latent form, which can be used as a method for  assessing  the  toxicity  of  a  drug  at  the stage of preclinical development.
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现代肝毒性药物对咖啡因排泄的影响
肝毒性物质是多种化学物质,可对特定器官产生破坏作用,这可能是它们直接作用于肝细胞和肝脏其他结构单元的结果。本研究的目的是评估现代肝毒性物质对咖啡因消除的影响。研究在圣彼得堡国立医科大学联邦国家预算高等教育机构药理学和毒理学系的活体动物馆中进行。不同化学组的工业物质被用来诱发肝中毒症状:邻苯二甲酸酐、乙二胺和氯仿。上述所有毒物的剂量均可立即(24 小时内)诱发肝中毒症状。 模拟实验结束一天后,按照之前一系列实验的方法,测定实验动物血清中咖啡因的含量,剂量为 100 毫克/千克,因为在这一剂量方案下,我们确定了咖啡因最稳定的药代动力学特征。 我们使用 STATISTICA 6.1 程序对所获得的数据进行了数理统计处理。 计算了算术平均数(M)及其平均误差(m);由于研究的探索性和缺乏比较组,没有使用学生检验来计算差异的显著性(p)。根据所进行的研究,我们可以得出结论:每种肝毒性物质都有各自的特点,因此我们可以建议对不同类型的肝毒性(包括未表达的肝毒性)进行咖啡因检测。也就是说,即使在潜伏期,也可以通过这种方法诊断出肝脏毒性状况,这可以作为在临床前开发阶段评估药物毒性的一种方法。
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