Theophilline and N-acetylcysteine (NAC) are preparations most often prescribed for protracted diseases of the respiratory system, such as bronchial asthma or chronic bronchitis. Written sources discussing theophilline and NAC do not contain any information on whether these preparations affect one of the most essential processes – ketogenesis - and if they do, in what way it happens. There is also no information on whether the preparations are hepatotoxic, despite the fact that it is recommended to minimize the dosage of both the chemical compounds in cases of any liver dysfunction.

Biotransformation of theophilline and acetyl cysteine takes place in the liver, accompanied by P-450 cytochrome isoenzymes. This may become a reason for hepatocyte metabolism disruption. Consequently, it can not be ruled out that these preparations disturb oxidative homeostasis in the liver, including ketogenesis.

The aim of this work was to assess metabolytic competence of isolated rat hepatocytes incubated in the presence of theophilline and/or N-acetylcysteine. The competence was measured by the intensity of ketogenesis.

The test was carried out using hepatocytes isolated by enzymatic method employing collagenase IV obtained from the livers of Wistar breed rats.The hepatocyte suspensions were incubated on “Hepatocyte Medium” base with the addition of theophilline and NAC. They were placed in Type BB 16 Heraeus incubator at the temperature of 37 C in CO₂ atmosphere.

After 30 and 120 minute incubation period the concentrations of ketone bodies – acetoacetate and β-hydroxybutyrate were measured by means of tests produced by Wako GmbH Neuus, Germany. Also, the ratio between mole concentrations of acetoacetate and β- hydroxybutyrate (KBR) was calculated.

The observed changes in concentrations of ketone bodies indicate the interference of both the preparations in the course of ketogenesis and, by that, in the physiological balance between the reduced and the oxidated form of nicotineamideadenine dinucleotide. In consequence, the presence of N-acetylocysteine in the hepatocyte base resulted in the rise in KBR value, regardless of the incubation time. On the other hand, theophilline, which, as the time of incubation passed and the doses increased, caused lowering of acetyloacetate concentration and increase in the concentration of β-hydroxybutyrate. This resulted in lowering of KBR value.

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