engleski

Ethanolic extract of propolis exacerbates copper-induced neuronal death: the involvement of ROS/p53/p38 interactions

Increased levels of copper are considered as contributing factor in the progression of neurodegenerative diseases by promoting oxidative stress conditions. The aim of our study was to examine effects of ethanolic extract of propolis (EEP) against copper-induced death in cultured P19 neuronal cells. Propolis is a heterogeneous resinous product collected by honey-bees. Due to its well documented health beneficial effects, including antioxidative and neuroprotective, propolis and its extracts are widely used in traditional and modern medicine. Surprisingly, we found that small, per se non-toxic concentrations of EEP exacerbated copper-induced death of P19 neurons. The neurotoxic effect of small concentrations of EEP was particularly pronounced in severe oxidative stress. In the presence of excess copper EEP increased production of reactive oxygen species (ROS) and stimulated caspase-3/7 activity. EEP also promoted copper-induced increase in the expression of transcription factor p53 and its downstream target Bax. The detrimental effects of EEP were accompanied with a prominent up-regulation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a metabolic enzyme that may sense oxidative stress and participate in cell death events. SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK) completely prevented toxic effects of EEP in severe oxidative stress conditions, whereas SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), demonstrated a significant pro-death effect. Our data indicates a pro-oxidative and apoptotic mode of EEP action in the presence of excess copper, and suggest an important role of ROS/p53/p38 crosstalk in death cascade. Although propolis is considered as a safe natural remedy, the obtained results pointed out that caution is required during its prolonged consumption in certain medical conditions. Our study also emphasized that detailed pharmacological and toxicological studies must be carried out for propolis and other natural dietary supplements in order to identify the entire repertoire of their undesirable side-effects.

Ethanolic extract of propolis ; Neurotoxic ; Oxidative stress, p53 ; p38

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