Synthesis of a silymarin-gold nanoparticle conjugate and analysis of its liver-protecting activity

Background: The liver disease problem prompts investigators to search for new methods of liver treatment. Introduction: Silymarin (Sil) protects the liver by reducing the concentration of free radicals and the extent of damage to the cell membranes. A particularly interesting method to increase the bioavailability of Sil is to use synthesized gold nanoparticles (AuNPs) as reagents. The study considered whether it was possible to use the silymarin-AuNP conjugate as a potential liver-protecting drug. Method: AuNPs were conjugated to Sil and examine the liver-protecting activity of the conjugate. Experimental hepatitis and hepatocyte cytolysis after carbon tetrachloride actionwere used as a model system, and the experiments were conducted on laboratory animals. Result: For the first time, silymarin was conjugated to colloidal gold nanoparticles (AuNPs). Electron microscopy showed that the resultant preparations were monodisperse and that the mean conjugate diameter was 18–30 nm ± 0.5 nm (mean diameter of the native nanoparticles, 15 ± 0.5 nm). In experimental hepatitis in mice, conjugate administration interfered with glutathione depletion in hepatocytes in response to carbon tetrachloride was conducive to an increase in energy metabolism, and stimulated the monocyte–macrophage function of the liver. The results were confirmed by the high respiratory activity of the hepatocytes in cell culture. Conclusion: We conclude that the silymarin-AuNP conjugate holds promise as a liver-protecting agent in acute liver disease caused by carbon tetrachloride poisoning.

CHARACTERISTICS OF FREE RADICAL LIPID PEROXIDATION AND ITS CONNECTION WITH IRON EXCHANGE IN EXPERIMENTAL HEPATITIS THERAPY

The purpose of the work is to study the processes of free radical lipid peroxidation, antioxidant system activity and their connection with the iron metabolism in white rats with experimental hepatitis, and after the use of hepatoprotectors. Materials and Methods. Studies were conducted on white Wistar rats: body weight – 180–200 g, age – 3 months. “Berlition” and “Legalon M” were administered intramuscularly, 0.2 ml per animal once a day (30 days). The authors registered the content of malonic dialdehyde (MDA), diene conjugates, catalase activity, serum iron level, total and unsaturated iron binding capacity. Results. In experimental animals, the level of diene conjugates increased 1.8 times if compared with healthy ones. After the administration of “Legalon M” and “Berlition”, the concentration of diene conjugates decreased by 58.6 % (by half) compared with the experimental animals. It was established that the malondialdehyde content significantly increased in all tissues. After the administration of “Legalon M” and “Berlition”, the malondialdehyde content decreased in the liver, lungs and muscle tissues. In the tissues of the intestine and in the blood serum, MDA level resolved to that of healthy animals. In experimental animals, catalase activity increased significantly if compared with healthy ones. After “Legalon M” and “Berlition” administration there was a decrease in enzyme activity in all body tissues. In animals with experimental hepatitis, there was a failure of iron metabolism in the body. The authors observed activation of iron metabolism in the body after drug administration to rats with experimental hepatitis. Conclusions. “Ligalon M” and “Berlition” have an antioxidant effect and stimulate iron metabolism. Keywords: hepatitis, antioxidants, free radicals, malonic dialdehyde, catalase, diene conjugates, iron metabolism, transferrin, lipids.