Antioxidant and detoxifying activities of analogues of the delta sleep inducing peptide

Abstract

16 DSIP analogues with substitutions of 1-2 amino acid residues were synthesized in order to investigate their potential use in medicine. Antioxidative properties of these peptides were studied in vitro and their detoxifying activity was examined in vivo on a model of toxicosis that was induced by the cisplatin cytostatic, which has been widely used in the cancer treatment. Practically all the studied DSIP analogues were shown to exhibit considerable direct antioxidative activity (AOA), and that of the ID-6 analogue was higher than AOA of DSIP and comparable with AOA of vitamin C and β-carotine. This analogue also demonstrated the most pronounced detoxifying effect towards cisplatin action, resulting in a decrease in the animal death from the acute cisplatin toxicity to 17% (in comparison with 50-67% for the control animals) and restoration of a number of cisplatin-sensitive biochemical blood parameters: decrease in the activity of aspartate aminotransferase and alanine aminotransferase and downregulation of the concentration of the final products of nitrogen exchange (creatinine and urea). Thus, the DSIP-relative peptides could be promising agents for the decrease in the toxic effects of cytostatics that are used in oncology.