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Neurotox Res ; 40(6): 2061-2071, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36435924

RESUMO

COA-Cl, a novel adenosine-like nucleic acid analog, has recently been shown to exert neuroprotective effects and to increase dopamine levels both in vivo and in vitro. Therefore, we hypothesized that COA-Cl could protect dopaminergic neurons against toxic insults. Thus, the present study aimed to investigate the protective effects of COA-Cl against hydrogen peroxide (H2O2)- and 6-hydroxydopamine (6-OHDA)-induced toxicity in PC12 cells and to elucidate the possible mechanisms. PC12 cells were incubated with COA-Cl (100 µM) with or without H2O2 or 6-OHDA (200 µM) for 24 h. Treatment with COA-Cl attenuated the decrease in cell viability, SOD activity and the Bcl-2/Bax ratio caused by H2O2. In addition, COA-Cl attenuated the increase in LDH release, ROS production, caspase-3 activity, and apoptosis induced by H2O2. Further, COA-Cl enhanced the protection of PC12 cells against the toxicity caused by 6-OHDA, as evidenced by an increase in cell viability and the Bcl-2/Bax ratio, and a decrease in LDH release. Our results are the first to demonstrate that COA-Cl potentially protects PC12 cells against toxicity induced by H2O2 and 6-OHDA, implying that COA-Cl could be a promising neuroprotective agent for the treatment of Parkinson's disease.


Assuntos
Peróxido de Hidrogênio , Fármacos Neuroprotetores , Ratos , Animais , Oxidopamina/toxicidade , Células PC12 , Peróxido de Hidrogênio/toxicidade , Estresse Oxidativo , Antioxidantes/farmacologia , Proteína X Associada a bcl-2 , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fármacos Neuroprotetores/farmacologia , Sobrevivência Celular
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