New tendencies of proteolysis/fibrinolysis pharmacological modulation with experimental Alzheimer’s disease

Abstract

Abstract. Nowadays effective methods to prevent and treat Alzheimer’s disease are lacking, therefore exploration of new tendencies concerning pathogenic therapy of the disease remains of topical interest. The fact that evaluation of biochemical condition of the damaged organs and systems assumes investigation of proteolysis/fibrinolysis markers deserves attention, since changes of the markers are considered as pathophysiological basis of many diseases and as a target of protective therapy. Therefore, objective of our study was to examine the effect of carbacetam, GABA-receptors modulator, and enalapril, angiotensin-converting enzyme inhibitor, on the proteolytic and fibrinolytic activity of the cerebral cortex and hippocampus of rats with Scopolamine-induced Alzheimer’s disease. The experiments were conducted on nonlinear laboratory albino male rats with their body weight of 0.18-0.20 kg. Alzheimer's disease was simulated by administration of scopolamine hydrochloride (Sigma, USA) at a dose of 1 mg/kg for 27 days. Carbacetam and enalapril were administered intraperitoneally at a dose of 5 mg/kg and 1 mg/kg, once daily for 14 days. The indices of proteo- and fibrinolytic activity were determined in the homogenates of the cerebral cortex and hippocampus. Under conditions of Scopolamine-induced Alzheimer’s disease proteolytic and fibrinolytic activity of the cerebral cortex and hippocampus of rats was found to increase. After carbacetam was administered to rats with Alzheimer’s disease during 14 days, collagenolysis and enzymatic fibrinolytic activity in the cerebral cortex decreased, and low molecular proteinolysis – in the hippocampus only. Under enalapril effect proteolysis/fibrinolysis indices decrease in both structures of the brain examined. The results obtained confirm participation of the proteolytic and fibrinolytic systems in the mechanisms of neurodegeneration, and are indicative of reasonability to initiate pathogenic correction by means of the modulators of renin-angiotensin and GABA-systems under conditions of Alzheimer’s disease development.