Elimination of 1,3,7-trimethyl-xanthine in laboratory animals during induction of toxic hepatitis

Abstract

Liver pathologies have a significant impact on caffeine clearance, which deserves serious attention and research. In the case of liver pathologies, the processes of caffeine metabolism are significantly modified; however, according to the scientific literature, the vector of such transformations for specific pathologies has not been determined. This is due to the fact that hepatopathy reduces the activity of enzymes responsible for caffeine metabolism. In some cases, an increase in caffeine clearance may occur, which is associated with a temporary compensatory activation of certain enzymes that may be involved in caffeine metabolism. Also, the clearance of caffeine may be reduced due to a decrease in the metabolic activity of the liver, which will significantly slow down its final excretion. To determine changes in the clearance of 1,3,7-trimethylxanthine, the most appropriate is to study its pharmacokinetic parameters, in particular, to compare its concentration in the blood serum in the phases of initial growth, plateau and decline with further construction of graphs - “caffeine curves”. The purpose of the study was to determine changes in serum caffeine levels during the induction of toxic hepatitis. 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. In order to simulate toxic hepatitis, experimental animals were intragastrically injected with a 35% oil solution of carbon tetrachloride (CCl4) daily for 5 days at a dosage of 1.5 ml/kg. Upon completion of induction, toxic hepatitis was confirmed based on clinical and biochemical signs. A day after the completion of the modeling of toxic hepatitis, the levels of caffeine in the blood serum were determined in the experimental animals in full accordance with the previous series of experiments. As a result of the study, “caffeine” curves were constructed, indicating increased caffeine concentrations in serum, increased elimination time, as well as an extremely long plateau in the concentration of caffeine in the blood serum during toxic liver damage.