RESUMO
The effect of administration of 3-acetylpyridine (antivitamin B3), on rat brain serotoninergic and NAD receptor systems was investigated. The injection of 3-acetylpyridine to rats caused a decrease of NAD and serotonin content in the brain and changes in [U-14C]NAD binding to synaptic membranes, serotonin uptake by nerve endings, as well as sensitivity of this process to NAD (10-5 M). Pretreatment of animals with nicotinamide restored modulating effect of NAD.
Assuntos
Encéfalo/efeitos dos fármacos , NAD/metabolismo , Piridinas/farmacologia , Serotonina/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/ultraestrutura , Masculino , Niacinamida/antagonistas & inibidores , Niacinamida/deficiência , Niacinamida/farmacologia , Ligação Proteica , Ratos , Ratos Wistar , Membranas Sinápticas/metabolismo , Sinaptossomos/metabolismoRESUMO
Streptosotocin-induced diabetes in rats is accompanied by the development of diabetic complications such as neuropathies. [2-14C]serotonin and [U-14C]GABA release from the neurotransmitter pre-loaded synaptosomes showed significant elevation. Aldose reductase inhibitors (AL-1576, sorbinil) administration leads to partial restoration of serotonin and GABA release, while picamilon restored only GABA release. It was shown that Na+,K(+)-ATPase activities decreased in synaptosomes, synaptic membranes and sciatic nerve of diabetic rats compared to control. Administration of AL-1576 normalized Na+, K(+)-ATPase activity, while sorbinil and picamilon less effectively. Sorbitol level are increased in streptozotocin-diabetic rats as compared to control. The picamilon and aldose reductase inhibitors administration to diabetic rats is accompanied by the partial reduction of brain sorbitol level. The findings confirm the important role of picamilon and aldose reductase inhibitors in the prevention and treatment of diabetic neuropathy.
Assuntos
Aldeído Redutase/antagonistas & inibidores , Neuropatias Diabéticas/prevenção & controle , Inibidores Enzimáticos/uso terapêutico , Fluorenos/uso terapêutico , Hidantoínas/uso terapêutico , Nootrópicos/uso terapêutico , Ácido gama-Aminobutírico/análogos & derivados , Animais , Encéfalo/metabolismo , Neuropatias Diabéticas/metabolismo , Masculino , Ratos , Ratos Wistar , Serotonina/metabolismo , Sorbitol/metabolismo , Sinaptossomos/metabolismo , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
Streptozotocin-induced diabetes in rats is accompanied by development of diabetic complications such as neuropathies. It was shown that aldose reductase inhibitors (A1-1576, sorbinil and unithiol) administration partially normalized not only polyol pathway. Aldose reductase inhibitors partially restored Na+, K(+)-ATP-ase activity in sciatic nerve of diabetic rats and redox state of nicotinamide adenine dinucleotides. The sorbitol level increases in streptozotocin-diabetic rats as compared to control. Administration of aldose reductase inhibitors to diabetic rats is accompanied by partial reduction of sorbitol level in sciatic nerve. The results obtained confirm the important role of a dose reductase inhibitors, as antidiabetic drugs, in the improvement of diabetic neuropathy.