Protective effects of thymogen analogues, modified by D-alanine, in hydrazine liver damage

Abstract

Introduction: It is known that the insertion of D-amino acids into the structure of a peptide molecule can increase its half-life. The pharmacological drug Thymogen was modified with D-alanine from the N- and C-terminus of the molecule. The aim of the investigation was to study the reparative and antioxidant activity of structural analogues of thymogen in toxic liver damage by hydrazine in rats. Materials and Methods: The investigation was conducted on 40 Wistar rats. Acute toxic liver damage was simulated with a single intraperitoneal injection of hydrazine hydrochloride at a dose of 50 mg/kg. Thymogen and its modified D-Ala analogues were administered intraperitoneally in equimolar doses for 5 days after intoxication. The animals were removed from the experiment 12 hours after the final administration of the peptides. Results and Discussion: It has been established the reparative and antioxidant activities of thymogen structural analogues increased in conditions of liver damage with hydrazine. Peptides with the insertion of D-Ala reduced the level of free radical reactions more significantly in comparison with thymogen. All peptides comparably increased catalase activity in blood plasma and liver homogenate. Conclusion: Thymogen analogues modified with D-Ala from the N- and C-terminus of the molecule can be considered as promising pharmacological substances for the development of new hepatoprotective drugs.

Keywords

• thymogen
• d-alanine
• toxic liver damage
• hydrazine
• reparative activity of hepatocytes
• free radical oxidation
• catalase