RESUMEN
Prion mRNA translation inhibition by antisense oligodeoxynucleotides (asODN) incorporated into immunoliposomes was investigated. It was shown that asODN complementary to cap region, start-codon region and a part of open reading frame can decrease the prion expression by 80% in L1210 cell line and by 60% in prion-replicating organs of laboratory rats. These results give grounds for further research asODN to be used as a means of prevention and treatment of prion infections.
Asunto(s)
Oligodesoxirribonucleótidos Antisentido/uso terapéutico , Proteínas PrPC/biosíntesis , Enfermedades por Prión/prevención & control , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Línea Celular Tumoral , Codón Iniciador/genética , Intestino Delgado/efectos de los fármacos , Intestino Delgado/metabolismo , Leucemia L1210 , Liposomas , Ratones , Oligodesoxirribonucleótidos Antisentido/administración & dosificación , Oligodesoxirribonucleótidos Antisentido/farmacología , Proteínas PrPC/genética , Ratas , Bazo/efectos de los fármacos , Bazo/metabolismoRESUMEN
It is established that except for already known influence of pentosan polysulphate (SP-54) on the expression of pathological prion, this preparation has an inhibiting effect in respect of physiological prion. Moreover, the reduction of concentration of physiologycal prion is registered in the central and peripheral organs of the prion-replicating system. It was also shown that inhibition of the studied protein leads to the growth in copper and zinc concentration in the proper organs and tissues, but at the same time activity of Cu/Zn-dependent superoxide dismutase does not change.
Asunto(s)
Poliéster Pentosan Sulfúrico/farmacología , Proteínas PrPC/antagonistas & inhibidores , Animales , Fragmentación del ADN/efectos de los fármacos , Immunoblotting , Masculino , Especificidad de Órganos , Proteínas PrPC/biosíntesis , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
We investigated the influence of L-arginine, a nitric oxide precursor, on the state of hemoglobin and basic parts of the antioxidant system. We revealed the negative influence of NO hyperproduction on the oxygen transport by haemoglobin, which is manifested by the increase of MetHb concentration and decrease of the MetHb-reductase activity. Also increase of glutathioneperoxidase, glutathionereductase and glutathion-etransferase activities were documentated; at the same time catalase activity in the erythrocyte hemolisate was decreased. This can point on the dominating role of glutathione in the protection of erythrocyte membrane and hemoglobin under the condition of oxidative stress, which was induced by NO hyperproduction.
