OXIDATIVE AND NITROSATIVE STRESSES ON THE TRANSLATIONAL MODEL OF DIABETES; NORMALIZING EFFECT OF Pro-Gly-CONTAINING DIPEPTIDE, NOOPEPT

R.U. Ostrovskaya, T.A. Antipova, N.N. Zolotov, S.V. Nikolaev, I.O. Logvinov, I.V. Ozerova, T.A. Gudasheva, S.B. Seredenin
V.V. Zakusov Institute of Pharmacology, Baltiyskaya str. 8, Moscow, 125315, Russian Federation
Е-mail: rita.ostrovskaya@gmail.com

Introduction. Oxidative and nitrosative stresses are reported to be an important pathogenic factors of diabetes. Taking into account our previous findings that Noopept (N-phenyl-acetyl-L-prolyl-glycine ethyl ester) attenuates the hyperglycemia, decrease of incretine GLP-1, loss of body weight, caused by diabetogenic toxin, streptozotocine (STZ), this study was undertaken in order to reproduce this translational model of diabetes and to study the effect of noopept on the indices of oxidative and nitrosative stresses. Methods. Experiments have been performed on Wistar rats, treated with single doses of STZ 40 mg/kg i.p. Noopept was administered in doses of 0,5 mg/kg starting on day 14th after STZ administration and was continuing for 14 days. Standard biochemical methods have been used for the determination of oxidative and nitrosative stresses parameters. Results. Besides of hyperglycemia, hypoinsulinemia, loss of body weight, STZ provoked the increase of MDA, NO level, of adenosine deaminase activity in blood plasma. STZ causes also the increase of iNOS activity in pancreas and liver. Noopept was shown to prevent all above listed indices of oxidative and nitrosative stresses. Conclusion. The mechanisms underlying these effects of Noopept are discussed. The involvement of its HIF-positive effect proposed as a triggering factor.
Keywords: 
Noopept, diabetes, HIF-1, oxidative and nitrosative stresses, rats