RESUMO
The influence of citicoline, phenylpiracetam, pentoxifylline and N-phenylacetyl-L-prolylglycine on cognitive processes and functional state of mitochondria in the neocortex of alloxan-diabetic rats has been studied. The drug effects on cognitive processes were assessed using passive avoidance tests in the dark-light camera. Latent period and the number of animals with amnesia skill on 6th and 20th days of drug administration were recorded. Functional status of mitochondria was assessed by mitochondrial pore opening and mitochondrial transmembrane potential (Y) on 20th day. It has been established that course administration of phenylpiracetam, citicoline and to a lesser extent N-phenylacetyl-L-prolylglycine, but not pentoxifylline, improves the processes of learning and storing conditional skill. At the same time, the nootropic activity of studied drugs was comparable to their effect on the functional state of mitochondria in neocortical neurons in rats with chronic hyperglycemia. According to mitoprotective activity (prevention of opening of mitochondrial cyclosporin-A-sensitive pores and restoration of mitochondrial transmembrane potential), the maximum potential was observed for citicoline and phenylpiracetam, and the minimum--for pentoxifylline. The results point out the importance of mitoprotective properties in nootropic effects of studied drugs.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Citidina Difosfato Colina/farmacologia , Dipeptídeos/farmacologia , Mitocôndrias/efeitos dos fármacos , Nootrópicos/farmacologia , Pentoxifilina/farmacologia , Piracetam/análogos & derivados , Aloxano , Amnésia/complicações , Amnésia/tratamento farmacológico , Amnésia/fisiopatologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Cognição/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Hiperglicemia/fisiopatologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Proteínas de Transporte da Membrana Mitocondrial/agonistas , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Piracetam/farmacologia , Ratos , Ratos WistarRESUMO
It has been established that prolonged alloxan-induced hyperglycemia in rats potentiates amnesic properties of scopolamine hydrobromide. It was characterized by shortening of the latent period by 44% (p<0,01) and by 47,7% (p<0,05) after 24 hours and on the 20th day of conditioned passive avoidance test. This effect was accompanied by increase in oxidative modification of proteins and nitric oxide synthesis in the cerebral cortex. Along with this, a significant enhancement of ADP- and collagen-induced platelet aggregation was observed. These processes may play the leading role in the development of cognitive deficit in diabetes. Meanwhile, co-administration of piracetam with acetylsalicylic acid was accompanied by an expressed antiamnetic potential - the reduction of early markers of proteins degradation (aldehydephenylhydrazones, APH) by 21,7% (p<0,05) and late markers of proteins degradation (ketonephenylhydrazones, KPH) by 23,8% (p<0,001) was noted. This combination was 15,7% (p<0,05) more active than piracetam according to the effect upon KPH. NO2-/NO3- level was also decreased by 30,3% (p<0,05) in comparison with alloxan-diabetic rats. The significant anti-platelet effect was observed: degree of collagen-induced platelet aggregation was reduced by 56,8% (p<0,01), ADP (5 µmol/l)-induced - by 31,7% (p<0,01), ADP (20 µmol/l)-induced - by 47,3% (p<0,01) as compared to the hyperglycemic rats. Such an increase in nootropic activity of piracetam may be assumed to be directly related to the ability of acetylsalicylic acid to improve microcirculation in the ischemic areas of the brain in diabetes and probably to its neuroprotective potential.
Assuntos
Amnésia/tratamento farmacológico , Aspirina/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Memória/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Piracetam/farmacologia , Amnésia/etiologia , Amnésia/fisiopatologia , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Masculino , Inibidores da Agregação Plaquetária/farmacologia , Ratos , Ratos WistarRESUMO
The effects of nootropic drugs (noopept, pentoxifylline, piracetam, pramiracetam, Ginkgo biloba extract, entrop, cerebrocurin and citicoline) on platelet aggregation in rats with experimental diabetes have been studied. It is established that all these drugs exhibit an inhibitory action of various degrees against platelet hyperreactivity under conditions of chronic hyperglycemia. The maximum universality of the antiaggregatory action is characteristic of pramiracetam, entrop and Ginkgo biloba extract.