Circadian peculiarities of antioxidant and membrane-protective properties of glutargin in acute chrono-determined paracetamol-induced hepatitis

Abstract

Hepatobiliary system diseases take a leading position among diseases of the gastrointestinal tract. One of the main groups of drugs used for their treatment is hepatoprotectors. Active development of chronophysiology, chronopatology and chronopharmacology creates the possibility of determining chronoportraits of drugs. Considering the latter it allows significantly optimizing the pharmacotherapy. Aim. To assess the circadian dependence of the antioxidant and membrane-protective activity of glutargin. The choice of the drug as the object of our study was made due to its frequent use in clinical practice. Materials and methods. The study was conducted on the model of acute paracetamol-induced hepatitis in the following chronosimulated mode: in the morning (09.00), in the daytime (15.00), in the evening (21.00) and at night (03.00). The dose of paracetamol in the experiment was 1000 mg/kg in rats. Glutargin was administered in the therapeutic and preventive mode in the dose of 135 mg/kg, i.e. an hour before administration of paracetamol and 2 hours after it. Results. The study conducted revealed the peculiarities of dysinchronosis of the prooxidant-antioxidant balance and the activity of cytolysis markers depending on the period of the day, in which paracetamol-induced hepatitis was simulated; it allowed determining the peculiarities of their correction with glutargin. The most distinct decrease in the AlAT and AsAT activity when using glutargin was observed against the background of night and day simulation of hepatitis. It is probably due to the circadian peculiarities of antioxidant and membrane-stabilizing properties of this drug. Conclusions . The circadian regulation peculiarities of prooxidant-antioxidant balance obtained with glutargin against the background of paracetamol-induced hepatitis should be considered when developing a comprehensive chronoportrait of this drug.