engleski

Prooxidative effect of flavonols in copper-induced oxidative stress

Neurodegenerative diseases are characterized by the progressive loss of specific populations of neurons. Oxidative stress (OS), induced by increased accumulation of reactive oxygen species (ROS), is one of the pivotal mechanisms underlying the common pathophysiology of these diseases. OS may be induced by disturbed homeostasis of transient metal ions that initiate production of ROS. Based on their ability to act as ROS scavengers and metal chelators, natural polyphenolic compounds are appreciated as potential neuroprotective agents. We investigated effects of flavonols quercetin and myricetin against copper-induced neuronal death in human neuroblastoma cell line SHSY5Y and P19 neurons. In both cellular systems, flavonols were capable to exacerbate toxic effects of copper and promote death. In P19 neurons, effects of quercetin were determined by the severity of neuronal injury. In moderate OS, quercetin exerted neuroprotective effect by attenuating ROS production, expression of PUMA and downstream apoptotic events (caspase-3 activation, nuclear condensation). During the severe oxidative insult, quercetin demonstrated prooxidative effect detrimental for neuronal survival. In neuroblastoma cells, only prooxidative action of myricetin was observed ending in caspase-independent programmed cell death and necrosis. Treatment with myricetin increased changes in chromatin condensation and damage of the plasma membrane. At the protein level, myricetin upregulated expression of PARP-1 and decreased expression of antiapoptotic protein Bcl-2. Atomic force microscopy revealed myricetin- induced changes of morphological (cell surface) and nanomechanical properties (roughness, elasticity). Hence, further studies should be carried out to better characterize possible side effects of prolonged supplementation with flavonols, particularly in conditions accompanied with metal-induced OS.

Flavonols ; Copper ; Oxidative stress ; Antioxidants ; Pro-oxidative activity

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