ORIGINAL RESEARCH
Effects of His-Phe-Arg-Trp-Pro-Gly-Pro peptide on free-radical oxidation processes in conditions of chronic restraint stress
1 Kursk State Medical University, Kursk, Russia
2 Institute of Molecular Genetics, RAS, Moscow, Russia
Correspondence should be addressed: Anton O. Vorvul
Karl Marx str. 3, Kursk, 305041, Russia; ur.liam@6991luvrov
Author contribution: Vorvul AO — performing experiments, quantification of oxidative stress markers, data acquisition and statistical processing, manuscript writing; Bobyntsev II — study concept and design, manuscript writing; Medvedeva OA — study concept and design; Azarova YuE — quantification of oxidative stress markers; Belykh AE — manuscript writing; Andreeva LA — study concept and design, peptide synthesis.
Compliance with ethical standards: the study was approved by the Ethics Committee of the Kursk State Medical University (protocol № 3 dated November 16, 2020). All the experiments were in line with the ARRIVE guidelines and were performed in accordance with the Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes.
Studying the effects of regulatory peptides on the stress-induced shifts in the bodily processes is of great fundamental and applied significance. Currently, a wide range of peptide neurotropic drugs, affecting the stress response development, are used in medicine, and new promising molecules are being studied. The study was aimed to assess the effects of the adrenocorticotropic hormone (ACTH) synthetic analog, ACTH(6-9)-Pro-Gly-Pro, administered at a dose of 5, 50 and 500 μg/kg, on the free-radical oxidation processes in Wistar rats, subjected to chronic restraint stress (CRS) during two weeks. Serum levels of 8-oxo-2'-deoxyguanosine (8-OHdG) and superoxide dismutase 3 (SOD3) were assessed by enzyme immunoassay, and the levels of thiobarbituric acid reactive substances (TBARS) were assessed by fluorimetric method. CRS lead to the significant increase in the 8-OHdG levels by 18.4% (p = 0.01) and the decrease in the SOD3 levels by 14.3% (p = 0.01), however, it had no effect on the levels of TBARS. ACTH(6-9)-Pro-Gly-Pro, administered at a dose of 5 and 50 μg/kg, significantly decreased the levels of 8-OHdG by 19.8% (p = 0.03) and 30% (p = 0.001), respectively. Thus, it was found that CRS resulted in oxidative stress in animals. ACTH(6-9)-Pro-Gly-Pro administration at a dose of 5 and 50 μg/kg inhibits the stress-induced free-radical oxidation processes.
Keywords: oxidative stress, regulatory peptides, His-Phe-Arg-Trp-Pro-Gly-Pro, ACTH(6-9)-Pro-Gly-Pro, free-radical oxidation, chronic restraint stress