SYNTHESIS OF POLYAMINES IN TOXIC HEPATITIS AS A PREDICTOR OF THE PROTECTIVE EFFECT OF L-ORNITHINE L-ASPARTATE
DOI:
https://doi.org/10.11603/mcch.2410-681X.2025.i1.15420Keywords:
polyamines; L-ornithine L-aspartate; hepatoprotector; hepatitis; cytolysis; cholestasisAbstract
Introduction. Polyamines are involved in many fundamental processes of cell growth and survival.Intracellular levels of polyamines depend on the activity of biosynthetic and catabolic enzymes and the status of transporters. Their synthesis is impaired under conditions of liver damage. L-ornithine L-aspartate (LOLA) is a mixture of endogenous amino acids with proven hepatoprotective effects. After decarboxylation, L-ornithine participates in the synthesis of polyamines and acts as a regulator of this process.The aim of the study is to establish the role of polyamine synthesis in the mechanism of the protective effect of L-ornithine L-aspartate in acute hepatitis.Research methods. The study was conducted on 48 white sexually mature non-linear male rats with an initial weight of 170–180 g. Acute toxic hepatitis was induced by a single intraperitoneal injection of tetrachloromethane at a dose 2 g/kg as a 50% oil solution. LOLA was administered at a dose of 200 mg/kg, and D, L -α difluoromethylornithine (DFMO) – 25 mg/kg for 2 days intraperitoneally, once a day. The study was carried out on the 3rd day after hepatitis modeling. The material for the study was liver, blood serum.Results and discussion. The following changes were observed in animals with acute toxic hepatitis: a reduction in the content of putrescine in liver homogenates, a pronounced augmentation in liver mass, an increase in the activity of aminotransferases, alkaline phosphatase, gamma-glutamyltransferase, a raise in the content of total bilirubin and total cholesterol in serum and a decrease in the concentrations of urea and total protein in the blood and in the liver. Correction with LOLA contributed to the prevention of the development of cytolysis and cholestasis, improved the synthetic function of the liver. The use of DFMO reversed all of the listed effects of LOLA.Conclusions. In acute toxic hepatitis in rats, polyamine synthesis is suppressed, but correction with LOLA improves the polyamine-synthesizing function of the liver. The use of the polyamine synthesis blocker DFMO reversed most of the effects of LOLA in preventing the development of pathological changes, in particular, the processes of cytolysis and cholestasis, and contributed to the deterioration of the synthetic function of the liver, which indicates a polyamine-dependent mechanism of the protective effect of L-ornithine L-aspartate in acute hepatitis.
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