Elimination of 1,3,7-trimethylxanthine in laboratory animals during the induction of fatty hepatosis

Abstract

Liver pathologies play a significant role in changing the metabolism and clearance of a number of pharmacologically active substances, including 1,3,7-trimethylxanthine, which is explained by their influence on enzyme systems that regulate the biotransformation of exogenous biologically active substances. Currently, changes in caffeine clearance are being actively studied in various hepatobiliary disorders, especially those that are chronic, since it is precisely such pathologies, according to a number of researchers, that are characterized by the most predictable and stable change in the trimethylxanthine pharmacokinetic profile. The purpose of the study was to determine changes in serum caffeine levels when inducing fatty liver disease in laboratory animals (rats). 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. Laboratory animals from a previous series of experiments were selected for the study in order to further compare the “caffeine curves.” Fatty hepatosis was modeled using strontium sulfate according to the methodology developed at the Department of Pharmacology and Toxicology. Upon completion of induction, fatty hepatosis was confirmed based on clinical and biochemical signs. Based on the studies conducted, we can conclude that there are certain correlations. For example, in fatty hepatosis, the elimination of caffeine is not significantly slowed down with a characteristic long plateau (up to 8 hours after administration), turning into a smooth decrease in concentration. Experimental data can be used to create a database to assess the relationship between pharmacokinetics and the physiological state of animals. Similar experiments need to be carried out on other animal species, which will create a holistic picture and help in assessing pathologies for veterinary specialists.