[CIRCADIAN DEPENDENCE OF PARACETAMOL HEPATOTOXICITY IN RATS.]

Results of chronopharmacological study of the circadian dependence of paracetamol toxicity and the extrapolation of obtained results to determine peculiarities in the daily activity of metabolic processes in rat liver are reported. The study was conducted on the model of acute paracetamol-induced hepatitis in both male and female rats in four diual periods: 03.00 a.m., 09.00 a.m., 15.00 p.m., and 21.00 p.m. The toxicity of paracetamol and the functional activity of liver were estimated by changes in markers of cytolytic activity of alanine aminotransferase (AIAT) and aspartate aminotransferase (AsAT) in blood serum, and the content of reduced glutathione (RG) in liver tissue. It is established that the degree of paracetamol toxicity and the level of hepatocyte RG are mutually dependent: the higher the content of RG in cells, the less pronounced toxic effect of xenobiotic is and vice versa, which is confirmed by correlation analysis (r = 0.43 - 0.94, depending on the circadian system of animals from control group). Extrapolation of results on the toxicity of paracetamol was used to reveal periods of the maximum and minimum functional activity of the liver. Acrophase of the functional activity of liver in rats corresponds to 15.00, and the antiphase of this activity in humans, to 01 - 03.