Regulatory peptides protect brain neurons from hypoxia in vivo

Abstract

Short peptides that have been characterized in previous studies performed in the St. Petersburg Institute of Bioregulation and Gerontology of the Northeastern Division of the Russian Academy of Medical Sciences [1‐3] protect neurons from oxidative stress [4]; however, under in vitro conditions, the peptide action has been observed at high (millimolar) concentrations. The anti-oxidant activity of these peptides is not high; therefore, their biological effect could be mediated by a natural system of antioxidant defense [5]. If this is the case, the peptide protective effect could be observed at almost physiological concentrations under the in vivo conditions. This was aimed at verifying this assumption. The protective effect of short regulatory peptides (vilon, epitalon, pinealon, and vesugen) was studied under the conditions of oxidative stress caused in animals by hypobaric hypoxia. Male Wistar rats weighing 185‐200 g were used in our experiments. Oxidative stress was induced under the conditions of hypobaric hypoxia in an altitude chamber with adjustable airflow, which prevented hypercapnia [6]. By means of a vacuum pump, the pressure in the altitude chamber was reduced to 0.125 atm for 1 min. Under these conditions, the animals were kept until respiration arrest; after this, the animals were returned to the normal-pressure conditions by supplying air into the chamber for 1 min. The following parameters were recorded: the time (s) until the respiration arrest “at the height”; the time (s) of posture recovery, i.e., the period from respiration arrest to the moment when the experimental animal assumed normal posture after “descending from the height” and respiration recovery under normobaric conditions; and the restitution time (s), the total duration of the recovery of physiological activity after hypoxia. To determine the protective effect of the peptides studied, the death rate and coefficient of restitution (the ratio of the restitution time to the time before respiration arrest in the altitude chamber) were estimated. The results obtained were processed statistically using the Mann‐Whitney and Kruskal‐Wallis tests; the differences were assumed to be significant at p < 0.05. The peptides vilon (Lys-Glu), vesugen (Lys-GluAsp), pinealon (Glu-Asp-Arg), and epitalon (Ala-GluAsp-Arg) were injected daily at a dose of 10 µ g/kg body weight intraperitoneously for five days before hypoxia. The rats of the control group were injected with saline according to the same scheme. Each group contained 10 animals.