CHRONOPHARMACOLOGICAL FEATURES OF SILIMARIN’S HEPATOPROTECTOCAL ACTIVITY UNDER PARACETAMOL HEPATITIS IN RATS

Abstract

Determination of dependence of the efficiency and toxicity of drugs on the time of day or season is one of the most promising areas of modern experimental and clinical pharmacology. The aim of the study. Aim is to identify features of daily rhythms of silymarin influence on the state of antioxidant/prooxidant and cytolytic processes (the leading link in the implementation of hepatoprotective activity) with paracetamol in rats under conditions of acute toxic liver damage. Materials and methods. Chronopharmacological action features of silymarin were studied by use of the generic drug "Karsil" as an example (Sopharma, Bulgaria) with paracetamol in rats under conditions of acute toxic liver damage. The state of the processes of POL-AOS was evaluated by the content of TBA-active products (TBA-AP), the content of recovered glutathione, the activity of SOD, catalase in hepatocytes, and the cytolytic processes by the activity of ALT in serum. Results. There was established a certain chronoarchitectonics of the rhythms of the antioxidant protection system and the activity of the processes of peroxidation in rats under physiological conditions, which was not disturbed by paracetamol on the background of acute liver damage (with the exception of level of acrophase catalase activity). The same dynamics and commonality of rhythms occurred on the background of the use of silymarin. The maximum display of silymarin hepatoprotective activity was observed under conditions of its use in the morning (09.00) and in the evening (21.00). Conclusions. The use of silymarin during periods of maximal display of its hepatoprotective activity, in the morning (09.00) and in the evening (21.00) may be the way to increase its bioavailability. Chronopharmacological features of silymarin activity have been established and should be taken into account when to conduct its further chronopharmacological studies.