As a consequence of enhanced production of oxygen free radicals, lipid peroxidation leads to the degradation of membrane lipids and disturbances of membrane permeability. Lipid peroxidation increases under stress conditions such as hypoxia, ischemia or acidosis as well as in metabolic diseases, e.g. diabetes mellitus. We have shown that subcomatous doses of insulin (6.0 IU/kg) significantly increase thiobarbituric acid reactive substances (TBARs), especially malondialdehyde (MDA) - the endproduct of lipid peroxidation, in the brain and heart of mice. In our model of insulin-induced hypoglycemia, mice were treated with the neuroprotective, peptide-containing drug Cerebrolysin (100 mg/kg b.w.). Animals were sacrificed by decapitation two or three hours after the injection of tested substance and samples were taken to determine several serum parameters (glucose, total protein, triglycerides and lactic acid) and TBARs in the brain and heart. Although Cerebrolysin was not able to affect serum parameters after subcomatous insulin injection, the drug significantly influenced lipid peroxidation. A single injection of Cerebrolysin already decreased TBARs levels in the brain and heart tissue. Presuming that an increase of TBARs reflects disturbances of the cell membrane, we have documented a promising effect of Cerebrolysin on cell integrity., J. Patočková, M. Kršiak, P. Marhol, E. Tůmová., and Obsahuje bibliografii
Application of Cerebrolysin (0.1 /rg per 1 ml) by a fast microperfusion system induced an inward current of 0.2 to 1 nA in all neurones from newborn mouse hippocampi held at —30 mV membrane potential. Cerebrolysin- induced currents were reduced by the GABAa antagonist bicuculline (2 /¿M) by 65 %, by the NMDA antagonist aminophosphovaleric acid (APV, 10 /¿M) by 27 %, and by the non-NMDA antagonist cyanonitroquinoxalinedione (CNQX, 10 ¡utA) by 20 %. Cerebrolysin dialyzed through a 3.6 kD gut did not induce any transmembrane current but potentiated the response induced by GABA (10 /utA) to 135 %. We conclude that, in addition to amino acids which activate GABAa, NMDA and non-NMDA receptors, Cerebrolysin also contains a peptide which potentiates the GABAa receptor response.