ABSTRACT
We studied the reparative and antioxidant effects of Thymogen and its new structural analogues obtained by binding amino acid D-Ala to the N- or C-end of the peptide molecule in acute toxic hepatopathy. Intragastric administration of carbon tetrachloride for 5 days caused the development of fat degeneration of hepatocytes, a decrease in catalase activity, and an increase in malondialdehyde concentration. Administration of peptides suppressed oxidative peroxidation and stimulated reparative regeneration of hepatocytes; Thymogen analogues produced more pronounced hepatotropic and antioxidant effects than Thymogen. Inclusion of D-Ala enhanced the effect of Thymogen on the processes of regeneration in hepatocytes and the antioxidant effect under conditions of acute carbon tetrachloride hepatopathy. The highest efficiency was achieved when the amino acid was added to the C-end of the molecule.
Subject(s)
Antioxidants , Chemical and Drug Induced Liver Injury , Humans , Antioxidants/pharmacology , Antioxidants/metabolism , Carbon Tetrachloride/toxicity , Liver/metabolism , Lipid Peroxidation , Peptides/pharmacology , Adjuvants, Immunologic/pharmacology , Models, Theoretical , Amino Acids/pharmacology , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/metabolismABSTRACT
Intraperitoneal administration of tripeptide Gly-His-Lys to male rats in doses of 0.5, 5, and 50 µg/kg 12 min before the start of the experiment produced an anxiolytic effect in the elevated plus maze test manifested in an increase in the time spent in open arms and shortened time spent in the closed arms. The anxiolytic effect was most pronounced after injection of 0.5 µg/kg peptide and decreased with increasing the dose of the peptide. Replacement of L-lysine with D-lysine in the tripeptide molecule was accompanied by a significant weakening of the neurotropic effects in all studied doses. Attachment of D-alanine to N- or C-terminus of Gly-His-Lys peptide leveled its anxiolytic action in all doses; significant changes in some measures of increased anxiety after administration at 50 µg/kg were found.
Subject(s)
Anti-Anxiety Agents/therapeutic use , Anxiety/drug therapy , Oligopeptides/therapeutic use , Animals , Anti-Anxiety Agents/administration & dosage , Male , Maze Learning/drug effects , Oligopeptides/administration & dosage , RatsABSTRACT
The mitotic index of hepatocytes remained unchanged after 10 intraperitoneal injections of DSLET and ACTH(4-10) in doses of 0.5, 1.5, and 5 microg/kg, but increased after injection of these substances in doses of 50 and 150 microg/kg. DSLET in doses of 5, 50, and 150 microg/kg decreased the number of antibody-producing cells in the spleen. ACTH(4-10) possessed immunosuppressive activity not only in these doses, but also in a dose of 1.5 microg/kg. As differentiated from mitotic activity of hepatocytes, the degree of immunosuppression increased with increasing the dose of test peptides.
Subject(s)
Adrenocorticotropic Hormone/pharmacology , Antibodies/metabolism , Enkephalin, Leucine/analogs & derivatives , Enkephalin, Leucine/pharmacology , Hepatocytes , Mitosis/physiology , Peptide Fragments/pharmacology , Analgesics/pharmacology , Animals , Dose-Response Relationship, Drug , Hepatocytes/drug effects , Hepatocytes/physiology , Mice , Mice, Inbred CBA , Nootropic Agents/pharmacologyABSTRACT
Ten intraperitoneal injections of tripeptide Gly-His-Lys in doses of 1.5, 5, 50, 150, and 450 mg/kg stimulated mitotic activity of hepatocytes and dose-dependently suppressed immune reactivity (number of antibody-producing cells and delayed-type hypersensitivity reaction).
